Repeating patterns of higher highs and holding support show bulls continue to succeed – but a break of mid-September support would be the first sign of failure
Despite concerns that a stock-market correction is imminent, repeating patterns of success by bulls show the uptrend is still intact – for now.
Those who believe a stock-market correction is imminent may have plenty of reason to do so, except the one thing that may matter the most for chart watchers – failure.
That’s why the S&P 500’s SPX 6,550 level is so important in the short term. There’s a tendency to look at the benchmark stock index’s chart for a signal suggesting that its uptrend is ending – but around market tops, it’s often what the index couldn’t do that confirms a reversal. And despite credit worries, a prolonged government shutdown and renewed tariff fears – which recently triggered the S&P 500’s biggest one-day selloff in six months – the charts still suggest bulls are in control.
What needs to happen for bulls to lose confidence, and confirm that a correction is in the works, is that the S&P 500 has to start failing to make higher highs while failing to hold support.
“Going back to the end of April, there have been multiple instances that [the S&P 500] looked ready to roll over; each one appeared ominous and threatened to flip momentum from positive to negative,” wrote Frank Cappelleri, technical analyst at CappThesis LLC, in a note to clients. “So far, none of those setups have confirmed, though, and that includes the current potential bearish pattern taking shape now (so far).”
As the following chart shows, there are some S&P 500 behaviors that have repeated in those previous and current “instances” that continue to confirm the uptrend.
Each potential reversal area, defined by different colors in the above chart, has been above the previous area. And in each colored area, the second peak has been higher than the first.
What that shows is that bulls continue to succeed in making higher highs – and as the saying among charts watchers goes, there’s nothing more bullish than a new high.
Additionally, the chart support created by the low of the pullback from the first peak in each colored area was successful in stopping the decline from the second peak.
Basically, each time bulls bought the dip, they were rewarded with a higher high. And success breeds the confidence to keep buying.
In the current setup, what would “confirm” a correction in the works is if the S&P 500 falls below the mid-September low, at 6,550, before the index can make a higher high. So the key upside levels to watch while the S&P 500 stays above 6,550 is the Oct. 15 intraday high of 6,724.12 and the Oct. 9 record high of 6,764.58.
If support would give way first, it would create a modified version of the widely known reversal pattern referred to as a “head and shoulders” – with the key component of that pattern being that the second shoulder is below the head.
It would also end what the Dow Theory, which has remained relevant on Wall Street for more than a century, defines as an uptrend – a repeating pattern of higher peaks and higher troughs.
CappThesis’s Cappelleri wrote that if support gives way, the initial measured-move target would be 6,335. He derived that target by measuring the height of the previous pattern, from support to the record high – 215 points – and then subtracting that from the broken support level.
While that might not seem too worrisome, as it would mark a pullback of just 6.4% from the record close, Cappelleri noted that it would be nearly double the size of any pullback since the April lows.
A correction – which many on Wall Street define as a decline of 10% to 20% from a significant high – would start if the S&P 500 falls to 6,088.
Keep in mind, however, that another tenet of the Dow Theory is that a trend remains in place until it provides a clear signal that it has reversed.
“Again, this has not happened yet, but it’s a scenario we need to stay alert to, as a confirmed breakdown would clearly shift the market’s complexion in a meaningful way,” Cappelleri wrote.
Basically, investors shouldn’t play the correction card yet – but they should be prepared, so they can act fast if that signal flashes.
-Tomi Kilgore
This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal.
Investors can approximate the average market return by buying an index fund. While individual stocks can be big winners, plenty more fail to generate satisfactory returns. That downside risk was realized by PepsiCo, Inc. (NASDAQ:PEP) shareholders over the last year, as the share price declined 12%. That’s well below the market return of 16%. Zooming out, the stock is down 11% in the last three years. On the other hand, we note it’s up 8.8% in about a month.
So let’s have a look and see if the longer term performance of the company has been in line with the underlying business’ progress.
We’ve found 21 US stocks that are forecast to pay a dividend yield of over 6% next year. See the full list for free.
There is no denying that markets are sometimes efficient, but prices do not always reflect underlying business performance. One flawed but reasonable way to assess how sentiment around a company has changed is to compare the earnings per share (EPS) with the share price.
Unhappily, PepsiCo had to report a 20% decline in EPS over the last year. The share price fall of 12% isn’t as bad as the reduction in earnings per share. So the market may not be too worried about the EPS figure, at the moment — or it may have expected earnings to drop faster.
You can see how EPS has changed over time in the image below (click on the chart to see the exact values).
NasdaqGS:PEP Earnings Per Share Growth October 19th 2025
It might be well worthwhile taking a look at our free report on PepsiCo’s earnings, revenue and cash flow.
As well as measuring the share price return, investors should also consider the total shareholder return (TSR). The TSR incorporates the value of any spin-offs or discounted capital raisings, along with any dividends, based on the assumption that the dividends are reinvested. So for companies that pay a generous dividend, the TSR is often a lot higher than the share price return. In the case of PepsiCo, it has a TSR of -8.8% for the last 1 year. That exceeds its share price return that we previously mentioned. This is largely a result of its dividend payments!
Investors in PepsiCo had a tough year, with a total loss of 8.8% (including dividends), against a market gain of about 16%. However, keep in mind that even the best stocks will sometimes underperform the market over a twelve month period. Longer term investors wouldn’t be so upset, since they would have made 5%, each year, over five years. It could be that the recent sell-off is an opportunity, so it may be worth checking the fundamental data for signs of a long term growth trend. While it is well worth considering the different impacts that market conditions can have on the share price, there are other factors that are even more important. Even so, be aware that PepsiCo is showing 3 warning signs in our investment analysis , and 1 of those is a bit concerning…
If you would prefer to check out another company — one with potentially superior financials — then do not miss this free list of companies that have proven they can grow earnings.
Please note, the market returns quoted in this article reflect the market weighted average returns of stocks that currently trade on American exchanges.
Have feedback on this article? Concerned about the content?Get in touch with us directly. Alternatively, email editorial-team (at) simplywallst.com.
This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.
The ALEX trial (NCT02075840) represents one of the most pivotal studies in the evolution of treatment for anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC). The trial’s earlier findings led to the global approval of alectinib as the first-line standard of care, demonstrating significant improvements in progression-free survival (PFS) and central nervous system (CNS) disease control compared with crizotinib.
At the ESMO Congress 2025, investigators presented the final overall survival (OS) and duration of response (DoR) results from ALEX, alongside updated long-term safety findings. These mature data confirm the sustained clinical benefit of first-line alectinib over crizotinib, with remarkable long-term survival extending beyond 80 months in the overall population and consistent benefit across all CNS subgroups.
Methods
The ALEX study was a randomized, phase 3, open-label trial enrolling 303 patients aged ≥18 years with previously untreated, advanced ALK+ NSCLC. Participants were randomized 1:1 to receive either:
Alectinib 600 mg twice daily (BID), or
Crizotinib 250 mg BID,
administered until disease progression, unacceptable toxicity, withdrawal, or death.
Randomization was stratified by ECOG performance status (0–1 vs 2), race (Asian vs non-Asian), and baseline CNS metastases (yes vs no). Notably, crossover between treatment arms before disease progression was not permitted, ensuring the validity of survival comparisons.
The key secondary endpoints included overall survival (OS), duration of response (DoR), and safety.
Results
At the final data cutoff of April 28, 2025, a total of 152 patients had been assigned to alectinib and 151 to crizotinib. After a median follow-up of 53.5 months for alectinib and 23.3 months for crizotinib, the median OS was significantly prolonged with alectinib, reaching 81.1 months (95% CI, 62.3–not estimable) compared with 54.2 months (95% CI, 34.6–75.6) for crizotinib. This corresponds to a hazard ratio (HR) of 0.78 (95% CI, 0.56–1.08), reflecting a 22% reduction in the risk of death.
Extended Overall Survival and Crossover Considerations
At a median follow-up of 53.5 months for the alectinib arm and 23.3 months for the crizotinib arm, the 7-year overall survival (OS) rate reached 48.6 % with alectinib compared with 38.2 % with crizotinib, confirming a durable long-term benefit. The OS hazard ratio (HR 0.78; 95 % CI 0.56–1.08) favored alectinib, reflecting a clinically meaningful 22 % reduction in the risk of death. While the difference did not reach formal statistical significance, this is likely due to crossover of crizotinib-treated patients to subsequent ALK TKI therapy, a factor known to confound late-phase survival outcomes. These findings underscore the robustness of alectinib’s efficacy, even in the context of real-world treatment sequencing.
CNS Subgroup Analysis
A particularly compelling aspect of the ALEX trial is the long-term CNS efficacy of alectinib, a known CNS-penetrant ALK inhibitor.
Among patients with baseline CNS metastases and prior radiation, median OS was 92.0 months with alectinib vs 39.5 months with crizotinib.
In those with CNS metastases but no prior radiation, median OS was 46.9 months vs 23.7 months, respectively.
In patients without baseline CNS metastases, median OS reached 94.0 months vs 69.8 months, underscoring the durability of systemic and intracranial control with alectinib.
Duration of Response
The median duration of response (DoR) was 42.3 months (95% CI, 31.3–51.3) with alectinib compared to only 11.1 months (95% CI, 7.9–13.0) with crizotinib (HR 0.41; 95% CI, 0.30–0.56).**
This nearly fourfold improvement in DoR illustrates the sustained and deep responses achieved with alectinib, consistent with its superior CNS efficacy and tolerability profile.
Safety Profile
Alectinib demonstrated a favorable and manageable safety profile, consistent with prior analyses and its established global experience.
Median treatment duration was 28.1 months with alectinib versus 10.8 months with crizotinib, reflecting prolonged disease control.
Grade 3–5 adverse events (AEs) occurred in 57.9% (alectinib) and 57.6% (crizotinib) of patients.
Serious AEs were reported in 46.1% (alectinib) and 31.8% (crizotinib).
Treatment discontinuation due to AEs occurred in 17.8% vs 14.6%, respectively.
Importantly, no new or unexpected safety concerns emerged, affirming the long-term tolerability of alectinib in prolonged use.
Interpretation
The final analysis from the ALEX trial confirms that first-line alectinib delivers durable, clinically meaningful survival benefit over crizotinib, with median overall survival surpassing 6.5 years. These results are particularly striking given that crossover was not allowed before disease progression, ensuring that the OS benefit reflects true treatment effect rather than post-progression therapy influence.
Furthermore, the robust CNS efficacy of alectinib remains a defining feature, addressing one of the key unmet needs in ALK+ NSCLC—prevention and long-term control of brain metastases.
Patients with CNS involvement achieved median OS approaching 8 years when treated with alectinib, compared to just over 3 years with crizotinib, underscoring the clinical importance of CNS-active targeted therapy.
Long-Term Follow-Up and Analytical Considerations
The ALEX final OS analysis at ESMO 2025 provides the most mature survival data for any first-line ALK inhibitor to date. With a median follow-up exceeding four years, the survival curves for alectinib versus crizotinib remain distinctly separated, showing no late convergence, which supports the long-lasting disease control achieved with alectinib.
These results also emphasize the reliability of long-term ALK inhibition and suggest that continuous blockade of ALK signaling may delay the emergence of resistance mechanisms that typically limit the efficacy of earlier-generation TKIs.
From a methodological standpoint, the no-crossover design strengthens the validity of the OS findings by minimizing confounding from post-progression therapy. The consistent DoR benefit further supports the durable and deep responses achievable with alectinib.
The trial’s safety monitoring over more than five years confirms the absence of cumulative toxicity, reaffirming alectinib’s suitability for prolonged therapy. These findings collectively reinforce alectinib as the definitive first-line standard of care for patients with advanced ALK-positive NSCLC.
An objective response rate of 50.5% was observed with raludotatug deruxtecan across all dose levels in these patients in the phase 2 part of REJOICE-Ovarian01
Phase 3 part of REJOICE-Ovarian01 to evaluate 5.6 mg/kg dose of raludotatug deruxtecan versus investigator’s choice of chemotherapy
BASKING RIDGE, NJ AND RAHWAY, NJ, October 19, 2025 – Results from the phase 2 (dose optimization) part of the REJOICE-Ovarian01 phase 2/3 trial showed that raludotatug deruxtecan (R-DXd) demonstrated clinically meaningful response rates in patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer. These data were presented today during a late-breaking proffered paper session (LBA42) at the 2025 European Society for Medical Oncology (#ESMO25) Congress.
Raludotatug deruxtecan is a specifically engineered, potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed by Daiichi Sankyo and Merck (NYSE: MRK), known as MSD outside of the United States and Canada.
The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens, highlighting the need for new treatment options.3
A confirmed objective response rate (ORR) of 50.5% (95% confidence interval [CI]: 40.6-60.3) was observed in patients (n=107)with platinum-resistant ovarian cancer receiving raludotatug deruxtecan across three doses (4.8 mg/kg, 5.6 mg/kg and 6.4 mg/kg) as assessed by blinded independent central review (BICR). There were 3 complete responses (CRs) and 51 partial responses (PRs) seen, and a disease control rate (DCR) of 77.6% (95% CI: 68.5–85.1) was observed.
In patients receiving the 5.6 mg/kg dose (n=36), a confirmed ORR of 50.0% (95% CI: 32.9–67.1) was observed as assessed by BICR with two CRs (5.6%), 16 PRs (44.4%) and a DCR of 80.6% (95% CI: 64.0–91.8). Clinically meaningful tumor responses were seen irrespective of dose and across a range of CDH6 expression levels.
The safety profile of raludotatug deruxtecan observed in REJOICE-Ovarian01 is consistent with safety findings from the phase 1 trial with no new safety signals identified. Nausea, anemia, asthenia and neutropenia were the most common treatment-emergent adverse events (TEAEs) across all doses. Treatment discontinuations due to treatment-related TEAEs occurred in 8.3% (n=3), 0.0% (n=0) and 8.6% (n=3) in the 4.8 mg/kg, 5.6mg/kg and 6.4 mg/kg groups, respectively. Grade 3 or higher treatment-related TEAEs occurred in 27.8% (n=10), 30.6% (n=11), and 48.6% (n=17) of patients in the 4.8 mg/kg (n=36), 5.6 mg/kg (n=36), and 6.4 mg/kg (n=35) groups, respectively.
The most common TEAEs (≥10% of total population) in the 5.6 mg/kg cohort included nausea (69.4%), anemia (58.3%), asthenia (50.0%), neutropenia (44.4%), vomiting (33.3%), constipation (27.8%), decreased appetite (25.0%), thrombocytopenia (19.4%), AST increase (16.7%), diarrhea (16.7%) and leukopenia (13.9%). Four (3.7%) interstitial lung disease (ILD)/pneumonitis events were confirmed as treatment-related across all doses as determined by an independent adjudication committee. The majority of ILD events (one with 5.6 mg/kg, two with 6.4 mg/kg) were low grade (grade 1 or 2). One grade ≥3 (4.8 mg/kg) ILD event was reported. Based on these efficacy and safety results, the 5.6 mg/kg dose has been selected for the phase 3 part of the trial.
“When ovarian cancer becomes resistant to platinum-based chemotherapy, treatment options for patients become limited,” said Isabelle Ray-Coquard, MD, PhD, President, ENGOT (European Network of Gynecological Oncology Trial) Group, Trial Leader, National Group of Investigators on the Studies of Ovarian and Breast Cancer (GINECO), and Medical Oncologist, Centre Léon Bérard, Lyon, France. “These promising results from the first part of REJOICE-Ovarian01 suggest that raludotatug deruxtecan may have an important role in treating patients with platinum-resistant ovarian cancer and support further evaluation in the phase 3 portion of this trial.”
“In this dose optimization analysis, rapid responses with impressive disease control have been observed with raludotatug deruxtecan across a range of CDH6 expression levels,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “These results, which contributed to the recent Breakthrough Therapy Designation in the U.S., reinforce the potential for raludotatug deruxtecan to become a new treatment option for certain types of patients with platinum-resistant ovarian cancer.”
“While we have seen targeted treatment advancements and improved outcomes in ovarian cancer in recent years, there is still a high unmet need for additional options for patients,” said Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories. “CDH6 is highly expressed in ovarian cancer, which underscores the potential of raludotatug deruxtecan to make an impact.”
In September 2025, raludotatug deruxtecan was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of adult patients with platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancers expressing CDH6 who have received prior treatment with bevacizumab.
Median follow-up for the 4.8-mg/kg, 5.6-mg/kg and 6.4-mg/kg cohorts was 5.6 months (95% CI: 4.7–6.3), 5.6 months (95% CI: 4.6–5.8), and 5.2 months (95% CI: 4.9–5.8), respectively. A majority of patients (51.4%) in REJOICE-Ovarian01 received three prior lines of treatment, including bevacizumab (n=89; 83.2%), PARP inhibitor (n=75; 70.1%) and mirvetuximab soravtansine (n=3; 2.8%). As of the data cut-off of February 26, 2025, 66 patients (61.7%) remain on treatment with raludotatug deruxtecan.
Summary of REJOICE-Ovarian01 Results
Efficacy Measure
Raludotatug Deruxtecan Across 4.8, 5.6 and 6.4 mg/kg (n=107)
Raludotatug Deruxtecan 6.4 mg/kg(n=35)
Raludotatug Deruxtecan 5.6 mg/kg(n=36)
Raludotatug Deruxtecan 4.8 mg/kg(n=36)
Confirmed ORR, %(95% CI)1
50.5% (40.6–60.3)
57.1% (39.4–73.7)
50.0% (32.9–67.1)
44.4% (27.9–61.9)
CR, n (%)
3 (2.8%)
0
2 (5.6%)
1 (2.8%)
PR, n (%)
51 (47.7%)
20 (57.1%)
16 (44.4%)
15 (41.7%)
SD, n (%)
42 (39.3%)
10 (28.6%)
15 (41.7%)
17 (47.2%)
PD, n (%)
8 (7.5%)
4 (11.4%)
2 (5.6%)
2 (5.6%)
NE, n (%)
3 (2.8%)
1 (2.9%)2
1 (2.8%)3
1 (2.8%)2
DCR, % (95% CI)
77.6% (68.5–85.1)
77.1% (59.9–89.6)
80.6% (64.0–91.8)
75.0% (57.8–87.9)
TTR, weeks, median (range)
7.1 weeks (5.1–19.1)
7.2 weeks (5.3–19.1)
6.6 weeks (5.1–18.3)
7.1 weeks (5.4–18.7)
Data cutoff: February 26, 2025.
1As accessed by BICR. 2Patient had no adequate post-baseline tumor assessment by BICR per RECIST 1.1. 3Patient had no adequate post-baseline tumor assessment by BICR.
BICR, blinded independent central review; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SD, stable disease; TTR, time to response
About REJOICE-Ovarian01
REJOICE-Ovarian01 is a global, multicenter, randomized, open-label phase 2/3 trial evaluating the efficacy and safety of investigational raludotatug deruxtecan in patients with platinum-resistant, high-grade ovarian, primary peritoneal or fallopian tube cancer, with disease progression following at least one but no more than three prior lines of systemic therapy, including prior treatment with mirvetuximab soravtansine for those with documented high-folate receptor alpha expression. Maintenance therapy (e.g., bevacizumab, poly ADP-ribose polymerase [PARP] inhibitors) is considered part of the preceding line of therapy.
The phase 2 part of REJOICE-Ovarian01 is assessing the safety and tolerability of three doses of raludotatug deruxtecan (4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg) to identify the recommended dose for the phase 3 part of the trial. The primary endpoint of the phase 2 part of the trial is ORR as assessed by BICR. Key secondary endpoints include ORR as assessed by investigator, DoR, PFS and DCR – all assessed by both BICR and investigator.
The phase 3 part of REJOICE-Ovarian01 is assessing the efficacy and safety of raludotatug deruxtecan at the selected dose (5.6 mg/kg) compared to investigator’s choice of chemotherapy (paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan). The dual primary endpoints of the phase 3 part of the trial are ORR and PFS as assessed by BICR. Secondary endpoints include PFS and ORR as assessed by investigator, DoR and DCR as assessed by both BICR and investigator, and OS. Pharmacokinetic and biomarker endpoints also will be assessed in both parts of the trial.
REJOICE-Ovarian01 is expected to enroll approximately 710 patients across Asia, Europe, North America, and Oceania. For more information, please visit ClinicalTrials.gov.
About Ovarian Cancer
More than 324,000 women were diagnosed with ovarian cancer worldwide in 2022.4 The median overall survival for advanced ovarian cancer following recurrence can be as little as two years, with a five-year survival rate of 31.8% for those with distant stage disease.1,2
The introduction of targeted therapies has expanded treatment options and improved survival outcomes for some patients with ovarian cancer, but additional options are needed for patients with tumors that progress on available medicines.5 Between 70% and 80% of patients diagnosed with advanced ovarian cancer will experience disease progression following standard treatment with platinum-based chemotherapy regimens.3 For patients who develop platinum-resistant ovarian cancer, defined as disease progression less than six months after completion of last platinum-based chemotherapy, prognosis is particularly poor and treatment options are limited.6,7
About CDH6
CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, including ovarian tumors.8 An estimated 65% to 94% of patients with ovarian cancer have tumors that express CDH6.9,10,11 In addition, CDH6 expression is observed more frequently in high-grade serous carcinomas.9,10,11 There is currently no CDH6 directed medicine approved for treatment of any cancer.
About Raludotatug Deruxtecan
Raludotatug deruxtecan is an investigational, potential first-in-class CDH6 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, raludotatug deruxtecan is comprised of a humanized anti-CDH6 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
About the Daiichi Sankyo and Merck Collaboration
Daiichi Sankyo and Merck (known as MSD outside of the United States and Canada) entered into a global collaboration in October 2023 to jointly develop and commercialize patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck & Co., Inc., Rahway, N.J., USA will maintain exclusive rights. Merck & Co., Inc., Rahway, N.J., USA will be solely responsible for manufacturing and supply for gocatamig.
About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.
The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU®, a HER2 directed ADC, and DATROWAY®, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc., Rahway, N.J., USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo.
The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.
Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs. For more information, please visit www.daiichisankyo.com.
Merck’s Focus on Cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit www.merck.com/research/oncology.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA
This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2024, and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Media Contacts:
Merck
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(617) 519-6264
julie.cunningham@merck.com
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(609) 500-4714
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Daiichi Sankyo
Global/US Media:
Jennifer Brennan
jennifer.brennan@daiichisankyo.com
(908) 900-3183
Japan Media:
DS-PR@daiichisankyo.co.jp
(732) 594-1579
peter.dannenbaum@merck.com
Steven Graziano
(732) 594-1583
steven.graziano@merck.com
Daiichi Sankyo:
DaiichiSankyoIR_jp@daiichisankyo.com
References:
Shimokawa M, et al. J Cancer. 2018; 9(5):872.
National Cancer Institute. Cancer Stat Facts: Ovarian Cancer. Updated 2021. Accessed September 2025.
Pignata S, et al. Ann Oncol. 2017 Nov 1;28(suppl_8):viii51-viii56.
Global Cancer Observatory. Population Fact Sheet. Updated 2022. Accessed September 2025.
Kurnit K, et al. Obstetrics and Gynecology. 2021; 137(1): 108-121.
Davis, et al. Gynecological Oncology. 2014; Jun;133(3):624-31.
Mor G, et al. Cancer biology & therapy. 2011;11(8), 708–713.
Bartolome RA, et al. Mol Oncol. 2021 Jul; 15(7): 1849-1865.
Shintani D, et al. Gynecol Oncol. 2022;166(Suppl 1): S116.
– Results from the BL-B01D1-303 (NCT06118333) phase III trial presented in a late-breaking oral presentation at ESMO represents the first data readout for iza-bren from a registration enabling study in China
REDMOND, Wash., Oct. 19, 2025 /PRNewswire/ — SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, today announced positive topline results from the BL-B01D1-301 trial. The trial has met one of the dual primary endpoints (BICR-assessed ORR) as iza-bren has demonstrated a statistically significant and clinically meaningful improvement in BICR-assessed ORR in recurrent or metastatic NPC patients who had progressed after at least two prior lines of chemotherapy, including platinum-based chemotherapy and a PD-1/PD-L1 inhibitor. These results were presented today in a late-breaking oral presentation at the 2025 European Society of Medical Oncology (ESMO) Congress.
Iza-bren is a potentially first-in-class topoisomerase 1 inhibitor-based bispecific antibody-drug conjugate (ADC) which targets both epidermal growth factor receptor and human epidermal growth factor receptor 3 (EGFRxHER3). It is being developed by Biokin in China and jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of China.
Iza-bren has shown a BICR-assessed ORR of 54.6% vs. 27.0% (Odds Ratio 3.3; 95% confidence interval 1.9-5.8; p<0.0001). Median duration of response (DoR) was 8.5 months for iza-bren versus 4.8 months for physician’s choice of chemotherapy (Hazard ratio 0.43; 95% CI 0.22 to 0.83). Furthermore, median progression-free survival (PFS) was 8.38 months with iza-bren compared to 4.34 months for chemotherapy (hazard ratio of 0.44; 95% confidence interval 0.32-0.62). The ORR and PFS benefits were consistent across all subgroup analysis. At the time of this analysis, the overall survival (OS) data were immature.
Iza-bren was well-tolerated with a manageable safety profile. The most common adverse events were hematological toxicities, which were effectively managed with standard supportive care. Two patients in the iza-bren arm experienced Grade 2 interstitial lung disease (ILD), whereas two patients in the chemotherapy arm experienced Grade 3 ILD. The safety profile in the BL-B01D1-303 study was consistent with the known profiles of the therapy with no new safety signals identified.
“The positive topline results from the first registrational trial of iza-bren presented at ESMO demonstrated clear clinical benefits of iza-bren compared to traditional chemotherapy. These data add to the growing body of clinical evidence that continues to reinforce our confidence in iza-bren’s mechanism of action and therapeutic potential. We believe iza-bren can deliver clinically meaningful benefit by targeting key cancer biological pathways to improve outcomes for patients across a broad range of advanced malignancies,” added Dr. Jonathan Cheng, Chief Medical Officer of SystImmune.
The New Drug Application (NDA) for iza-bren for the treatment of recurrent or metastatic nasopharyngeal carcinoma (NPC) has been submitted by Biokin to the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) in China.
About BL-B01D1-303
BL-B01D1-303 is a phase III, randomized, open-label, multicenter study in China to evaluate the efficacy and safety of BL-B01D1 in patients with recurrent or metastatic nasopharyngeal carcinoma who have failed PD-1/PD-L1 monoclonal antibody and at least two lines chemotherapy (one line must contain platinum-based chemotherapy). For more detailed information, please visit clinical.trials.gov (NCT06118333).
About Nasopharyngeal Carcinoma (NPC)
Nasopharyngeal Carcinoma (NPC) is a type of head and neck cancer that originates in the nose. NPC is uncommon globally, but is endemic in southern China, southeast Asia and parts of Africa, and is rising among the immigrant population in US and Europe. NPC is strongly associated with EBV infection. There is a significant unmet need as 5-year overall survival rate is generally less than 10% in the later line metastatic setting.
About iza-bren
SystImmune, in collaboration with BMS outside of China, is developing iza-bren (BL-B01D1), a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren’s dual mechanism of action blocks EGFR and HER3 signals to cancer cells, reducing proliferation and survival signals. In addition, upon antibody mediated internalization, iza-bren’s therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.
About SystImmune
SystImmune is a clinical-stage biopharmaceutical company located in Redmond, WA. It specializes in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs). SystImmune has several assets in various stages of clinical trials for solid tumor and hematologic indications. Alongside ongoing clinical trials, SystImmune has a robust preclinical pipeline of potential cancer therapeutics in the discovery or IND-enabling stages, representing cutting-edge biologics development.
Forward-Looking Statements
Any research and development information provided by SystImmune is intended for general information purposes only. Such information is not intended to provide complete medical information. We do not offer patient-specific treatment advice and if you have medical conditions, please see your medical doctor or healthcare provider.
This press release may contain forward-looking statements with the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, and the Private Securities Litigation Reform Act of 1995, which reflects the expectations regarding the company’s goals, strategies, results of operations, performance, business prospects, and opportunities, including but not limited to the ability to gain Investigational New Drug status for the resulting new product and the ability to develop a successful formulation. Terms such as “anticipates,” “believes,” “expects,” “estimates,” “could,” “intends,” “may,” “plans,” “potential,” “projects,” “will,” “would” and other similar expressions, or the negative of these terms, are generally indicative of forward-looking statements.
While SystImmune, Inc. believes that expectations expressed in the forward-looking statements are based on the company’s reasonable assumptions and beliefs in light of the information available to the company at the time such statements are made, it cannot give assurance that such forward-looking statements will prove to have been correct. Such forward-looking statements are not fact and are subject to uncertainties and other factors that could cause actual results to differ materially from such statements. We undertake no obligation to update any forward-looking statements contained in this press release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.
For additional information about the company, please visit https://systimmune.com/.
Q: Could you summarize the magnitude of benefit seen with Dato-DXd compared to chemotherapy in this first-line mTNBC population and comment on how clinically meaningful this is for practice? Rebecca Dent, MD: As we know, patients with metastatic triple-negative breast cancer—especially those who are not eligible for immune checkpoint inhibition, which represents about 60% to 70% of patients we see in the first-line setting—have had chemotherapy as the standard of care for well over 10 years. In this setting, 50% of patients progress and never go on to receive second-line therapy. So there was a real need to incorporate a novel therapy into the first-line setting.
In addition, patients are receiving more treatment in the curative setting, and so if they relapse, they’ve already seen a number of different chemotherapies. What’s unique about TROPION-Breast02 is that we are incorporating an antibody-drug conjugate as the first-line therapy in patients with relapsed or de novo metastatic TNBC, or those relapsing more than 12 months after initial therapy.
Here we saw the use of Dato-DXd, a TROP2-directed antibody-drug conjugate with a potent topoisomerase payload and a stable, cleavable linker. Because of the drug-to-antibody ratio, we see potent effectiveness in terms of improvements in progression-free survival (PFS), with a safety profile that allows administration every three weeks, which is very convenient for patients.
We saw an impressive improvement in PFS—from about 5 months to over 10 months in median PFS, a delta of more than 5 months. These Kaplan-Meier curves separate very early, with a time to treatment response of 1.4 months, and the curves continue to separate and remain sustained.
We also saw an improvement in overall survival (OS). Median OS was 18.7 months with standard chemotherapy and increased to almost 2 years with Dato-DXd—a delta of 5 months, with a statistically significant hazard ratio.
The data were very consistent. In clinic, what’s extraordinary is seeing such a visible improvement in response. We saw more than a doubling of response rates with Dato-DXd compared with chemotherapy—well over 60%, a delta of more than 30%, and a tripling of the complete response rate.
What’s even more helpful in clinic is that these responses are sustained. Often, we can achieve a response, but it doesn’t last. In this trial, duration of response increased from 7 months with chemotherapy to more than 12 months with Dato-DXd—again, a 5-month improvement. So across endpoints—PFS, OS, and duration of response—we consistently saw about a 5-month delta favoring Dato-DXd.
The addition of the PI3K/AKT/mTOR (PAM) inhibitor gedatolisib to fulvestrant (Faslodex), with or without palbociclib (Ibrance) led to clinically meaningful and statistically significant improvements in progression-free survival (PFS) among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA wild-type advanced breast cancer following progression on, or after, treatment with a CDK4/6 inhibitor and an aromatase inhibitor. 1,2
The benefits of PAM inhibition were seen in results from the phase 3 VIKTORIA-1 trial (NCT05501886) that were presented at the European Society for Medical Oncology Congress 2025.1 In addition to PFS, gedatolisib also showed gains in median duration of response (DOR) and incremental objective response rates (ORRs) compared with fulvestrant alone.
“VIKTORIA-1 is the first study to demonstrate a statistically significant and clinically meaningful improvement in progression-free survival with PAM inhibition in patients with PIK3CA wild-type disease, all of whom received prior CDK4/6 inhibitor,” Sara A. Hurvitz, MD, FACP, senior vice president and director, Clinical Research Division, Fred Hutch, said during a presentation of the data.
How significantly did gedatolisib improve PFS and other efficacy end points?
Compared with fulvestrant alone (arm C), both the triplet of gedatolisib, fulvestrant, and palbociclib (arm A) and doublet regimen of gedatolisib plus fulvestrant (arm B) induced superior PFS. The triplet reduced the risk of disease progression by 76% compared with fulvestrant alone (median PFS 9.3 months [95% CI, 7.2-16.6] vs 2.0 months [95% CI, 1.8-2.3], respectively; hazard ratio, 0.24; 95% CI, 0.17-0.35; P <.0001). The doublet reduced the risk of progression by 67% vs fulvestrant alone (7.4 months [95% CI, 5.5-9.9] vs 2.0 months [95% CI. 1.8-2.3], respectively; hazard ratio, 0.33; 95% CI, 0.24-0.48; P <.0001).
Superior median PFS was consistent across subgroup analyses for both the triple and doublet regimens. Most noteworthy, according to Hurvitz, was that patients who received prior palbociclib benefited from the triplet regimen. “This is the first time that data in the randomized setting suggested benefit to palbociclib rechallenge,” she said.
When comparing median PFS benefit between arms A and B, the triplet regimen demonstrated higher clinical benefit in almost all subgroups, including those who were pre/perimenopausal, endocrine therapy resistant, with visceral metastases, and for those who had previously received treatment with palbociclib.
At a data cutoff of May 30, 2025, data for overall survival (OS) were immature, with only 48% of the protocol specified events, Hurvitz noted. Compared with 18.5 months (95% CI, 15.8-NE) in the monotherapy arm, the triplet and doublet regimens, respectively, demonstrated a median OS of 23.7 months (95% CI, 21.4-not estimable [NE]; hazard ratio, 0.69; 95% CI, 0.43-1.12; P = .1328) and not reached (NR; 95% CI, NR-NR; hazard ratio, 0.74; 95% CI, 0.46-1.19; P = .2122).
Sixty-three patients in the fulvestrant arm crossed over to the triplet (n = 52; 48.1%) or doublet (n = 11; 10.2%) regimens. This could impact overall survival, Hurvitz said, adding that a sensitivity analysis performed at the time of crossover showed a greater separation of the OS curves in favor of the triplet (hazard ratio, 0.60; 95% CI, 0.35-1.04; P = .0698) and doublet (hazard ratio, 0.56; 95% CI, 0.33-0.97; P = .0393) regimens.
“The study is continuing to follow patients for overall survival, with final analysis is anticipated about 48 months after the first patient was randomized, or early 2027,” she added.
Tumor response was also superior in both the triple and doublet regimens, compared with fulvestrant alone.
In the triplet arm, the ORR was 31.5%. There was 1 complete response (CR), 38 partial responses (PRs), 67 patients with stable disease (SD), and 17 patients with progressive disease (PD). Further, the clinical benefit rate (CBR; defined as CR, PR, and SD >24 weeks) among this arm was 50%, with a disease control rate (DCR; defined as CR, PR, and SD) of 85.5%. The DOR was a median of 17.5 months (95% CI, 8.8-NE).
In the doublet arm, the ORR was 28.3%, with no CRs, 32 PRs, 55 with SD, and 26 with PD. CBR and DCR were 48.7% and 77.0%, respectively, with a median DOR of 12.0 months (95% CI, 8.1-NE).
Lastly, in the monotherapy arm, the ORR was 1.0%, with no CRs, 1 PR, 40 with SD, and 62 with PD. The CBR and DCR were 11.4% and 39.0%, respectively, with the median DOR not reached.
What is the safety profile of gedatolisib?
Treatment with gedatolisib was generally well tolerated in both arms with no new safety signals, according to Hurvitz.
In total, 3 patients in the triplet arm and 4 in the doublet arm discontinued treatment due to a treatment-related adverse event (TRAE). Two deaths occurred in the triplet therapy arm.
Treatment-related AEs of interest with the triplet and doublet regimens were stomatitis (any grade, 69.2% and 56.9%, respectively), rash (any grade, 27.7% and 32.3%), diarrhea (any grade, 16.9% and 12.3%), and hyperglycemia (any grade, 9.2% and 11.5%).
Why is PAM pathway investigation significant?
The PAM pathway drives breast cancer growth and contributes to endocrine and CDK4/6 inhibitor resistance; however, as most available therapies are indicated only for patients with PI3K-pathway activation, an unmet need remains for those with wild type disease.
“Therapeutic attempts to completely block the PAM pathway have been limited by toxicity,” Hurvitz explained. “Most available therapies target a single component of the pathway and have modest efficacy limited to biomarker selected patient populations.”
Following preliminary clinical activity of gedatolisib in combination with palbociclib and fulvestrant as a therapy in the second line and beyond among patients with HR-positive, HER2-negative advanced breast cancer, the investigators aimed to evaluate the highly potent multitarget PAM inhibitor in this patient population following progression on a CDK4/6 inhibitor and aromatase inhibitor.
What is the design of the VIKTORIA-1 trial?
In the open-label, randomized phase 3 trial, 392 patients were randomized 1:1:1 to receive either of the following regimens:
Triplet (arm A; n = 131): 180 mg IV gedatolisib once weekly for 3 weeks on and 1 week off, 125 mg palbociclib daily for 21 days and 7 days off, and 500 mg fulvestrant on days 1 and 15 in cycle 1, followed by every 4 weeks;
Doublet (arm B; n = 130): The same gedatolisib and fulvestrant dosing regimens as Arm A; or
Monotherapy/Control (arm C; n = 131): the same fulvestrant dosing regimen as used in the investigational arms.
Patients treated with fulvestrant monotherapy were allotted the option to cross over to arms A or B at progression.
Pre- and postmenopausal patients were eligible for the trial if they had progression on or after treatment with a CDK4/6 inhibitor and aromatase inhibitor, 2 or more lines of prior endocrine therapy for advanced breast cancer, measurable disease via RECIST v1.1, and a screening result for PIK3CA status. Patients were ineligible if they had type 2 diabetes mellitus with a glycated hemoglobin of greater than 6.4% or type 1 diabetes mellitus; prior therapy with an mTOR, PI3K, or AKT inhibitor; or chemotherapy treatment for their advanced breast cancer.
Patients were stratified by lung/liver metastases, time to progression on their immediate prior therapy, and region.
The co-primary end points were PFS in arm A compared with arm C and PFS in arm B vs arm C. Secondary end points included OS, ORR, safety, and quality of life.
Demographics and baseline characteristics were generally well balanced across treatment arms.
What is the future direction of gedatolisib?
“We are very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well-tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event,” said Igor Gorbatchevsky, MD, chief medical officer of Celcuity, in a press release.2
“This safety profile combined with the 7.3- and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens, offer potentially paradigm shifting results for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer,” he added.
According to the release, a rolling new drug application (NDA) has been submitted in tandem with the FDA’s Real-Time Oncology Review Program based on data from the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial. The NDA is expected to be completed before the end of 2025, and topline data from the trial is expected in the first half of 2026. The phase 3 VIKTORIA-2 trial (NCT06757634), designed to evaluate gedatolisib in the frontline setting, is ongoing.
References
Hurvitz SA, Layman RM, Curigliano G, et al. Gedatolisib Plus Fulvestrant, With & Without Palbociclib, vs Fulvestrant in Patients With HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer: First Results from VIKTORIA-1. Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA17.
Celcuity news release. Detailed Results from PIK3CA Wild-Type Cohort of Phase 3 VIKTORIA-1 Trial Presented at 2025 ESMO Congress Demonstrate Potential for Gedatolisib Regimens to be Practice Changing for Patients with HR+/HER2- Advanced Breast Cancer. October 18, 2025. Accessed: October 18, 2025. https://tinyurl.com/4x6w44nt
As a mother of two, Paige Harris has noticed a change in the way she shops for her family.
“Items that I have bought regularly have gone up in price steadily,” she said. “From hair dye to baby formula, our grocery list has gotten smaller while our budget has had to increase. Meats like steak are a no-go for our household.”
Harris, 38, lives and works as a teacher’s assistant in Stella, North Carolina, and is one of almost 40 people who spoke to the Guardian about how they’ve been coping with the price of goods in the six months since Donald Trump announced his sweeping tariffs.
On Thursday, a study from S&P Global revealed that companies were expected to pay at least $1.2tn more in 2025 expenses than was previously anticipated. But the burden, according to the researchers, is now shifting to US consumers. They calculated that two-thirds of the “expense shock”, more than $900bn, will be absorbed by Americans. Last month, the Yale Budget Lab estimated tariffs would cost households almost $2,400 more a year.
Harris says the tariffs’ impact on her daily life contradicts promises from the Trump administration to “cut prices and make living affordable for everyone”. She said: “You see prices soaring. It has become very clear that this administration did not and does not care about the everyday lives of Americans.”
Several Americans told the Guardian their weekly budgets had been drastically altered with the introduction of Trump’s tariffs.
“Prices are way too high. I mostly shop at Costco and buy as little as possible anywhere else,” said Jean Meadows, a 74-year-old retiree who lives in Huntsville, Alabama. “I can’t imagine that stores haven’t noticed the change. I think people are really afraid of what is coming.”
That sense of apprehension is reflected in a recent poll, exclusively conducted for the Guardian, where respondents identified the tariffs as the second biggest threat to the economy.
“The bread I buy has doubled in price within a year. We live on a fixed income that doesn’t keep up with inflation,” said Myron Peeler, who is also retired and is the sole caregiver for his wife, who suffers from debilitating arthritis. The only saving grace, he said, is that his house and car are paid off.
Trump shows few signs of backing away from his tariff policy – a move the White House maintains will reinvigorate American manufacturing and increased revenue from trade partners.
Most recently, the president reignited a trade war with China by threatening a 100% tariff on Beijing as soon as November. This came after China moved to restrict exports of rare earth minerals needed for several everyday items from electric vehicle batteries to hospital equipment, a decision that Trump branded as “very hostile”. In an interview with Fox News, the president has admitted that the proposed tariff hike was “not sustainable”, but said he was left with little choice: “They forced me to do that”.
Currently, the average US tariffs on Chinese exports hovers around 58%, according to the Peterson Institute for Economics. It’s a levy that is already taking a toll on Americans such as Michele, from north-eastern Pennsylvania.
“We need to buy new tires for a car, and can’t, because affordable tires are no longer in stock and we can’t afford $250 a tire,” she said.
Several people echoed Michele’s feelings about availability, describing the situation as “empty shelves, higher prices”. Natalie, who lives in New Hampshire, said she hasn’t seen certain pantry staples “for months”. She said: “The store shelves have become more and more bare … instead of multiple choices there may only be one or two, and name brands are being replaced by store brands.”
At 55, Natalie is semi-retired but is due to start part-time work at a supermarket, and she has seen a price rise in nearly everything she buys regularly. “Any brand of cat food has increased anywhere from 25% to double the price. One wet food my cats like went from $1.79 to $2.49 per can,” she said.
The new normal many Americans are bracing for, or already feeling, is not just the cost of groceries, for those such as Minnie, a food writer in Portland, Oregon, it’s a change in lifestyle.
“I don’t shop for non-essentials. No fall shopping trips for a new sweater or jeans. And we’ll make all our Christmas presents this year,” said Minnie, 55. “We used to dine out once a week. Now we never eat out. Even fast-casual is insanely pricey. Everything is twice what it used to cost and we’re very afraid of what’s next, financially speaking.”
While the US inflation rate hovers around 2.9% – a substantial drop from the spikes of the Covid era – the tariffs haven’t helped ease the impact on Americans’ wallets. Richard Ulmer, 81, who has lived in Florida for 35 years, said this year has been “the worst from a financial standpoint”, adding that “everything” from his groceries to the electric bill has become more expensive.
For Cassie, a 25-year-old consultant based in Siler City, North Carolina, costs have shot up quickly compared to the “gradual price increases” during the first two years of the pandemic. Cassie has a strict $65 per week budget for groceries, but since Trump first announced his tariffs, she’s been priced out of her normal routine, which included doing most of her weekly shopping at Walmart.
“Now I must visit at least four different stores in the area and other towns, often driving longer distances to find the best prices,” she said. “During the summer months and the Mexico/Latin America tariff announcement, Walmart and other stores in the area ran out of bananas for around two weeks. No one could get bananas in my area.”
Tencent Music Entertainment Group (NYSE:TME) shareholders might be concerned after seeing the share price drop 15% in the last month. But that doesn’t change the fact that the returns over the last three years have been spectacular. In fact, the share price has taken off in that time, up 484%. As long term investors the recent fall doesn’t detract all that much from the longer term story. The only way to form a view of whether the current price is justified is to consider the merits of the business itself.
With that in mind, it’s worth seeing if the company’s underlying fundamentals have been the driver of long term performance, or if there are some discrepancies.
We’ve found 21 US stocks that are forecast to pay a dividend yield of over 6% next year. See the full list for free.
To quote Buffett, ‘Ships will sail around the world but the Flat Earth Society will flourish. There will continue to be wide discrepancies between price and value in the marketplace…’ One way to examine how market sentiment has changed over time is to look at the interaction between a company’s share price and its earnings per share (EPS).
Tencent Music Entertainment Group was able to grow its EPS at 57% per year over three years, sending the share price higher. In comparison, the 80% per year gain in the share price outpaces the EPS growth. This indicates that the market is feeling more optimistic on the stock, after the last few years of progress. It’s not unusual to see the market ‘re-rate’ a stock, after a few years of growth.
The company’s earnings per share (over time) is depicted in the image below (click to see the exact numbers).
NYSE:TME Earnings Per Share Growth October 19th 2025
It is of course excellent to see how Tencent Music Entertainment Group has grown profits over the years, but the future is more important for shareholders. This free interactive report on Tencent Music Entertainment Group’s balance sheet strength is a great place to start, if you want to investigate the stock further.
When looking at investment returns, it is important to consider the difference between total shareholder return (TSR) and share price return. Whereas the share price return only reflects the change in the share price, the TSR includes the value of dividends (assuming they were reinvested) and the benefit of any discounted capital raising or spin-off. It’s fair to say that the TSR gives a more complete picture for stocks that pay a dividend. In the case of Tencent Music Entertainment Group, it has a TSR of 496% for the last 3 years. That exceeds its share price return that we previously mentioned. This is largely a result of its dividend payments!
We’re pleased to report that Tencent Music Entertainment Group shareholders have received a total shareholder return of 91% over one year. That’s including the dividend. Since the one-year TSR is better than the five-year TSR (the latter coming in at 9% per year), it would seem that the stock’s performance has improved in recent times. Someone with an optimistic perspective could view the recent improvement in TSR as indicating that the business itself is getting better with time. Before deciding if you like the current share price, check how Tencent Music Entertainment Group scores on these 3 valuation metrics.
But note: Tencent Music Entertainment Group may not be the best stock to buy. So take a peek at this free list of interesting companies with past earnings growth (and further growth forecast).
Please note, the market returns quoted in this article reflect the market weighted average returns of stocks that currently trade on American exchanges.
Have feedback on this article? Concerned about the content?Get in touch with us directly. Alternatively, email editorial-team (at) simplywallst.com.
This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned.
Neoadjuvant fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) yielded benefit in pathologic complete response (pCR) rates compared with dose-dense doxorubicin and cyclophosphamide plus THP (ddAC-THP) in patients with high-risk, HER2-positive early breast cancer, according to data from the phase 3 DESTINY-Breast11 trial (NCT05113251).1
Findings presented at the 2025 ESMO Congress demonstrated that patients treated with T-DXd followed by THP (n = 321) experienced a pCR rate of 67.3% compared with 56.3% for those given ddAC-THP (n = 320; difference, 11.2%; 95% CI, 4.0%-18.3%; P = .003). Notably, the pCR benefit was observed in the hormone receptor–positive population, where the pCR rate was 61.4% in the T-DXd arm (n = 236) vs 52.3% in the ddAC-THP arm (n = 235; difference, 9.1%; 95% CI, 0.2%-17.9%), as well as the hormone receptor–negative population, where the respective pCR rates for the T-DXd arm (n = 83) and ddAC-THP arm (n = 85) were 83.1% and 67.1% (difference, 16.1%; 95% CI, 3.0%-28.8%).
“DESTINY-Breast11 showed the highest reported pCR rate in HER2-positive early breast cancer for a registrational study in the neoadjuvant setting, despite—if you want to do cross-trial comparisons—a high prevalence of hormone receptor–positive disease and a high-risk population,” lead study author Nadia Harbeck, MD, PhD, said in a presentation of the data.
Harbeck is director of the Breast Center and chair for Conservative Oncology at the Department of OB&GYN at LMU University Hospital in Munich, Germany.
How Was the DESTINY-Breast11 Trial Designed?
Harbeck noted that current neoadjuvant standard-of-care (SOC) regimens for HER2-positive early breast cancer have remained unchanged for more than a decade. As such, investigators sought to evaluate T-DXd–based treatment in this population with the goal of improving efficacy and safety vs the current SOC.
The randomized, global, multicenter, open-label study enrolled patients with previously untreated HER2-positive early breast cancer who had high-risk disease, defined as ≥cT3 and N0-3 or cT0-4 and N1-3; or inflammatory breast cancer. Patients were allowed to enroll, irrespective of hormone receptor status.
Patients were randomly assigned in a 1:1:1 fashion to receive T-DXd followed by THP; ddAC-THP; or T-DXd alone, followed by surgery in all arms. In the first arm, patients received 4 cycles of T-DXd followed by 4 cycles of THP. In the second, ddAC was administered for 4 cycles, followed by 4 cycles of THP. In the final arm, patients received T-DXd alone for 8 cycles.
Notably, the T-DXd monotherapy arm was closed in March 2024, following a recommendation from the study’s independent data monitoring committee.
After surgery, study protocols called for the following treatments, irrespective of arm:
pCR: radiotherapy and concomitant trastuzumab with or without pertuzumab for up to 1 year
Non-pCR: radiotherapy and ado-trastuzumab emtansine (Kadcyla) for up to 14 cycles
The study’s primary end point was pCR rate (ypT0/Tis ypN0) per blinded independent central review (BICR) assessment. Secondary end points included BICR-assessed pCR rate (ypT0 ypN0), event-free survival (EFS), safety, pharmacokinetics, invasive disease-free survival, overall survival, and health-related quality of life. Residual cancer burden (RCB) was an additional outcome measured during the study.
At data cutoff, 16.9% of patients in the T-DXd plus THP arm discontinued a study drug, including T-DXd (2.8%), paclitaxel (14.4%), trastuzumab (2.2%), and pertuzumab (2.2%); 97.2% of patients in this arm proceeded to surgery. In the ddAC-THP arm, 13.8% of patients had discontinued any study treatment, including AC (2.9%), paclitaxel (12.0%), trastuzumab (3.0%), and pertuzumab (3.7%); 93.8% of patients in this arm underwent surgery. In the T-DXd monotherapy arm (n = 286), 18.4% of patients discontinued study treatment, and 95.8% underwent surgery.
Regarding post-neoadjuvant treatments, 99.1% of evaluable patients in the T-DXd arm who achieved a pCR (n = 226) underwent any adjuvant therapy, comprising any cytotoxic chemotherapy regimen (5.8%), any T-DM1–containing regimen (1.8%), and any trastuzumab-containing regimen (94.2%). In the ddAC-THP, 98.4% of patients who achieved a pCR (n = 190) underwent any adjuvant therapy, including any cytotoxic chemotherapy regimen (5.8%), any T-DM1–containing regimen (2.1%), and any trastuzumab-containing regimen (91.6%).
For patients who did not achieve a pCR, any adjuvant therapy was administered to 89.5% of patients in the T-DXd plus THP arm (n = 95) and 82.3% of patients in the ddAC-THP arm (n = 130). In the experimental group, adjuvant therapies included any cytotoxic chemotherapy regimen (10.5%), any T-DM1–containing regimen (52.6%), and any trastuzumab-containing regimen (38.9%). These respective rates were 9.2%, 56.9%, and 26.2% in the control group.
In the T-DXd plus THP and ddAC-THP arms, the median age was 50 years (range, 25-82) and 50 years (range, 23-79), respectively. All patients in both arms were female. The highest proportion of patients in each arm was from Asia (T-DXd plus THP, 47.4%; ddAC-THP, 47.5%) and were Asian (49.8%; 49.1%). Most patients had an ECOG performance status of 0 (86.6%; 87.5%), had immunohistochemistry 3+ HER2-positive disease (87.2%; 88.4%), had cT0-2 tumors (54.8%; 58.8%), and had positive lymph nodes (89.4%; 87.8%).
What Were the Other Efficacy Outcomes for T-DXd Plus THP vs ddAC-THP?
Findings also showed that 81.3% of patients in the T-DXd plus THP arm had no RCB (RCB-0) or minimal RCB (RCB-1) in resected breast or lymph node tissue compared with 69.1% in the ddAC-THP arm (difference, 12.2%). In the hormone receptor–positive population, the RCB-0 plus RCB-1 rates were 78.0% for T-DXd plus THP vs 64.7% for ddAC-THP; these respective rates were 90.4% and 81.2% in the hormone receptor–negative population.
Investigators also reported an EFS trend favoring T-DXd plus THP, with data at 4.5% maturity (HR, 0.56; 95% CI, 0.26-1.17). Maturity for the data cutoff of the trial’s final analysis is predicted at approximately 10%. The 24-month EFS rates were 96.9% (95% CI, 93.5%-98.6%) in the T-DXd plus THP arm vs 93.1% (95% CI, 88.7%-95.8%) in the ddAC-THP arm.
What Is the Safety Profile of T-DXd Plus THP?
Any-grade adverse effects (AEs) occurred in 98.1% of patients in the T-DXd plus THP arm compared with 98.7% of patients in the ddAC-THP arm. The respective rates of grade 3 or higher AEs were 37.5% and 55.8%. Any-grade serious AEs were reported in 10.6% and 20.2% of patients, respectively.
In the T-DXd plus THP arm, AEs led to dose any dose reduction, any drug interruption, and any treatment discontinuation in 18.1%, 37.8%, and 14.1% of patients, respectively. In the ddAC-THP group, these rates were 19.2%, 54.5%, and 9.9%, respectively. AEs led to death in 0.6% of patients in both arms. AEs led to delays in surgery in 3.4% of patients in the experimental arm vs 2.6% of patients in the control arm.
Regarding AEs of special interest, any-grade drug-related adjudicated interstitial lung disease (ILD) was 4.4% in the T-DXd plus THP arm vs 5.1% in the ddAC-THP arm. The rates of grade 3 or higher ILD were 0.6% and 1.9%, respectively. Grade 5 ILD occurred in 1 patient (0.3%) in both groups. Any-grade left ventricular dysfunction occurred in 1.3% of patients in the experimental arm vs 6.1% of patients in the control arm. The rates of grade 3 or higher left ventricular dysfunction were 0.3% and 1.9%, respectively, although no grade 5 events were reported in either group.
Any-grade treatment-emergent AEs reported in at least 20% of patients in either arm included nausea (T-DXd plus THP, 64.7%; ddAC-THP, 51.6%), diarrhea (58.8%; 54.2%), alopecia (47.5%; 49.0%), fatigue (41.3%; 54.8%), increased transaminase levels (34.4%; 33.7%), neutropenia (29.1%; 44.2%), constipation (29.1%; 24.4%), vomiting (28.8%; 21.2%), peripheral neuropathy (25.9%; 20.8%), anemia (22.8%; 49.7%), stomatitis (18.4%; 27.9%), and leukopenia (17.2%; 23.4%).
What Data Were Reported for T-DXd Monotherapy in HER2+ Early Breast Cancer?
When the T-DXd monotherapy arm, patients were allowed to remain on therapy or immediately switch to local SOC. If patients switched therapy, they were classified as having a non-pCR.
Findings from the monotherapy arm showed that patients (n = 286) achieved a pCR rate of 43.0% at the primary analysis and 51.4% at a prespecified supplementary analysis. EFS data were similar between T-DXd monotherapy and ddAC-THP (HR, 0.82; 95% CI, 0.41-1.62), and the 24-month EFS rate in the T-DXd monotherapy group was 94.4% (95% CI, 90.5%-98.7%).
Regarding safety, 97.5% of patients treated with T-DXd alone (n = 283) experienced any-grade AEs, 22.6% had grade 3 or higher AEs, and 10.2% had any-grade serious AEs. AEs led to dose reduction, drug interruption, and treatment discontinuation in 6.7%, 18.0%, and 7.8% of patients, respectively. One patient (0.4%) experienced an AE that led to death. AEs led to surgical delay in 6.4% of patients.
The rate of any-grade, drug-related adjudicated ILD was 4.9% in the T-DXd monotherapy arm, although all instances were grade 1 or 2. Left ventricular dysfunction occurred in 0.7% of patients, all at grade 1 or 2.
What’s Next for T-DXd Plus THP?
Based on data from DESTINY-Breast11, the FDA accepted a supplemental biologics license application seeking the approval of neoadjuvant T-DXd followed THP for the treatment of adult patients with high-risk, HER2-positive (IHC 3+ or in situ hybridization–positive), stage II/III breast cancer.2
The FDA has assigned a target action date of May 18, 2026, under the Prescription Drug User Fee Act.
“DESTINY-Breast11 results support T-DXd [plus] THP as a more effective and less toxic neoadjuvant treatment compared with ddAC-THP, and it may become the preferred regimen for patients with high-risk, HER2-positive early breast cancer,” Harbeck concluded in her presentation.1
Disclosures: Harbeck reported receiving honoraria from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Menarini Stemline, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Viatris, and Zuellig Pharma; serving as a consultant or advisor for Exact Sciences, Gilead, Pfizer, Roche, and Sandoz; having an institutional site contract with AstraZeneca; serving as a data safety monitoring board or advisory board member for Gilead, IQVIA, and Roche; and having ownership interested in the West German Study Group.
REFERENCES:
1. Harbeck N, Modi S, Pusztai L, et al. DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 291O.
2. Enhertu followed by THP supplemental biologics license application accepted in the U.S. for patients with high-risk HER2 positive early-stage breast cancer prior to surgery. News release. Daiichi Sankyo. October 1, 2025. Accessed October 18, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202510/20251001_E.pdf
