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First-line sacituzumab tirumotecan (sac-TMT) plus tagitanlimab (KL-A167) showed promising efficacy and safety for patients with advanced or metastatic non–small cell lung cancer, according to results from the phase 2 OptiTROP-Lung01 trial (NCT05351788) published in Nature Medicine.

In cohort 1A (n = 40), the median best percentage change in target lesions from baseline was –30.6% (range, –91.8% to 13.0%) and –44.8% (range, –89.6% to 0%) in cohort 1B (n = 63). The confirmed overall response rate (ORR) was 40.0% (95% CI, 24.9%-56.7%) in cohort 1A and 66.7% (95% CI, 53.7%-78.0%) in arm B. The disease control rate (DCR) was 85.0% (95% CI, 70.2%-94.3%) in cohort 1A and 92.1% (95% CI, 82.4%-97.4%) in cohort 1B.

The median progression-free survival (PFS) in cohort 1A was 15.4 months (95% CI, 6.7-17.9). The 6-month PFS rate was 69.2% (95% CI, 51.2%-81.6%), and the 12-month PFS rate was 51.1% (95% CI, 33.5%-66.2%). In cohort 1B, the median PFS was not reached (95% CI, 9.6-not estimable [NE]). The 6-month PFS rate was 84.2% (95% CI, 71.8%-91.4%) and the 12-month PFS rate was 58.4% (95% CI, 44.2%-70.1%).

“In this phase 2 study, the combination of sac-TMT and tagitanlimab exhibited encouraging efficacy and a manageable safety profile in patients with advanced or metastatic NSCLC in the first-line setting,” the authors of the study wrote. “These findings provide a rationale for further investigation of sac-TMT plus immunotherapy in a broad spectrum of patients with NSCLC, as evidenced by the increasing number of phase 3 studies evaluating this combination therapy.”

A total of 103 patients were enrolled. In arms 1A and 1B, the median age was 63 years in both cohorts, most patients were male (85.0% vs 76.2%), and 72.1% vs 60.3% had a smoking history. An ECOG performance status of 1 was noted in 97.5% of patients in cohort 1A and 85.7% in cohort 1B, brain metastases were observed in 12.5% and 3.2%, liver metastases in 10.0% and 14.3%, and squamous cell carcinoma was documented in 55.0% and 46.0%.

The coprimary end points of the trial included safety and ORR. Secondary end points included PFS, duration of response, and DCR according to RECIST v1.1 criteria.

In cohort 1A, sac-TMT was given at 5 mg/kg every 3 weeks plus tagitanlimab at 1200 mg every 3 weeks in each 3-week cycle. In cohort 1B, patients were given sac-TMT at 5 mg/kg every 2 weeks plus tagitanlimab at 900 mg every 2 weeks in each 4-week cycle.

Treatment-related adverse effects (TRAEs) in cohort 1A were observed in 95.0% of patients and in 96.8% in cohort 1B. Grade 3 or higher TRAEs were noted in 42.5% of patients in cohort 1A and 58.7% in cohort 1B.

Dose reductions of sac-TMT due to TRAEs were observed in 17.5% of patients in cohort 1A and 42.9% in cohort 1B. Treatment discontinuations due to any drug were observed in 2.5% and 6.3%, and discontinuation of sac-TMT was noted in 2 patients in cohort 1B, while tagitanlimab discontinuation occurred in 2.5% in cohort 1A and 3.2% in cohort 1B.

Treatment-related serious AEs occurred in 10.0% of patients in cohort 1A and 20.6% in cohort 1B.

The most common TRAEs of grade 3 or higher in cohort 1A and 1B, respectively were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%), anemia (5.0% and 19.0%), rash (5.0% and 7.9%), stomatitis (0% and 9.5%), and drug eruption (7.5% and 0%).

Immune-related AEs (irAEs) occurred in 25.0% of patients in cohort 1A and 39.7% in cohort 1B. Grade 3 or higher irAEs were noted in 7.5% of patients in cohort 1A and 12.7% in cohort 1B, with the most common between cohorts being rash (12.5% and 14.3%), increased alanine aminotransferase (ALT) (0% and 11.1%), hypothyroidism (2.5% and 7.9%), increased aspartate aminotransferase (AST) (0% and 6.3%) and hyperthyroidism (0% and 6.3%).

Reference

Hong S, Wang Q, Cheng Y, et al. First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial. Nat Med. Published online August 19, 2025. doi:10.1038/s41591-025-03883-5

Omar Nadeem, MD, Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Center for Early Detection and Interception of Blood Cancers at Dana-Farber Cancer Institute; Nausheen Ahmed, MD, a hematologist-oncologist and associate professor in the Division of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Cancer Center; and Forat G Lutfi, MD, an assistant professor in the Division of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Cancer Center, provided insights on the FDA’s decision to eliminate Risk Evaluation and Mitigation Strategies (REMS) requirements for all currently approved CD19- and BCMA-directed autologous CAR T-cell immunotherapies in hematologic malignancies.

This decision, which was announced on June 27, 2025, is expected to expand access to these therapies by reducing longstanding socioeconomic, geographic, and logistical barriers, experts explained when interviewed by OncLive®.

Watch the video or read the transcript below to learn more about how this regulatory change is expanding patient access by reducing monitoring requirements and logistical burdens, while also fostering the development of hybrid care models that integrate community oncology centers into the delivery of this curative therapy. For a more in-depth look at the factors informing the removal of this safeguard and its implications for real-world oncology practice, check out our feature article.

Nadeem: The REMS requirement is no longer there for CAR T-cell therapy, which is going to be huge. Before, that was one of the reservations patients had. They could not drive for 2 months. They needed a caregiver for [1] month. These things were real barriers [to CAR T-cell therapy]. To patients going forward with this therapy, it seems much more doable for the majority of patients and their caregivers. They can take that time to get through this, and then they can go back to their community.

Ahmed: When CAR T[-cell therapy first] emerged back in 2017, just a few centers were doing it. Now it has expanded, but we know that there’s [still] room for improvement. It’s not out there in the community. When the REMS [protocols] first came about, monitoring focused on cytokine release syndrome [CRS] and immune effector cell–associated neurotoxicity syndrome [ICANS].

Lutfi: Traditionally, REMS training is required for providers and for people who are interacting with patients, and that is a time and financial barrier. It is hard for a lot of smaller-scale centers to adopt any therapy like CAR T [when] those requirements and restrictions [are in place]. The additional monitoring time period was also quite restrictive. Most centers would keep people locally for 30 days, some a little less, but that was generally what has been done. Additionally, the driving requirements, which previously lasted 8 weeks, were also restrictive for patients and limited the ability for patients who just could not do that, whether it was getting groceries or whatever was required of them.

Ahmed: This regulatory change is a huge deal. It surprised many of us that it came so fast, and we were impressed with that. We have already started making progress toward implementing it. Patients are now able to drive after 2 weeks, as long as they are stable, and they are able to go back home as long as they are stable. We are involving our community oncologists and referring oncologists earlier, and they are willing to take it on. There is more flexibility, which we love, and the patients love it.

Lutfi: As we get more comfortable and we see all these safety parameters, the risk of truly getting high-grade CRS and ICANS after 2 weeks is quite low. Most studies show [an incidence of] less than 1% to 2% [after 2 weeks post-infusion]. As we see that things are being done more safely, we are going to keep reducing the requirements and hoops that patients and their caretakers have to jump through.

Our plan is to move step by step, starting with some of our affiliated community sites. I visit some of them, and that would allow the first rollout. What we are hoping to do is shift some of the preparation and work-up for CAR T—which usually takes weeks before infusion—into the community sites. That way, when patients need echocardiograms, imaging, or other work-up that we traditionally kept at the main campus, we can do it in the community. The infusion process will still be done at the main center.

We have been giving bispecific [antibodies] in the community for over 2 years now, and [community clinicians] are very comfortable. The patients selected for community rollout [of CAR T-cell therapy] will be lower-risk or average-risk patients. We are not saying every [patient getting] CAR T should be managed in the community. Patients with primary refractory disease or relapsed, very high–risk disease, with very high risk for toxicity and complications, should not be treated in the community. Patient selection is an important factor.

Nadeem: We are moving quickly to adopt these changes since the REMS requirements were dropped. To be honest, I do not think [toxicity management] is going to change too much, because most toxicities occur within that 2-week window [after infusion]. CRS usually occurs within a week and is typically resolved by day 14. If it is not, we keep the patient until it is resolved. The more acute neurological toxicities are also usually resolved by that time point. Delayed neurological toxicities can occur weeks to months later, so that is not affected by the monitoring window.

Nadeem: The CRS timeline is fairly reliable. We can see inflammatory markers rise, and when patients develop chills or other signs, we know CRS is coming. At that point, we typically admit them around day 7, and they may stay until day 10 or 11. That means they are in the hospital for 3 days instead of 10 days, which has made a big difference for patients.

As a result, we have had to make sure we have enough providers, lab monitoring, and nursing support. It takes a whole team effort to guide management of these toxicities. It has been very smooth, and I think it will only get better over time.

Ahmed: As referring oncologists get more comfortable with CAR T-cell therapy, they will hopefully advocate for it more, and we will likely see more patients treated with CAR T-cell therapy.

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The US could break its dependence on China for many critical minerals if metals found in the waste from existing American mines were used rather than discarded, new research has found.

The US is among a growing number of countries racing to secure more independent supplies of metals including copper, lithium and nickel — which are essential for a broad range of industries, from energy to technology and defence. 

China has invested heavily in the sector for two decades and dominates the supply chains for many critical minerals.

That dominance contributed to the Trump administration’s imposition of hefty tariffs on a range of Chinese products in a bid to encourage domestic US supply chains.

The paper, published in the journal Science on Thursday by researchers at the Colorado School of Mines, said that the US could supply most of its metals needs if it made better use of mining waste.

“The US’ vulnerable supply of critical minerals is not a function of domestic geological availability,” they said. Recovering even small quantities of the byproducts “would substantially reduce net import reliance for most critical minerals,” said the researchers. 

The waste from the 54 mining operations active in the US were likely to be rich in many of the critical minerals needed by the country’s industrial sector, they added.

Their analysis found that recovering some of the metals that occur as byproducts at active mines, combined with existing production, could be “sufficient to meet US manufacturing demand for copper, iron, molybdenum, silver, nickel, zinc and [rare earths].” 

Making better use of these waste products could prove difficult, however, since the researchers noted that “a lot more research, development and policy” was needed to make it “economically feasible”.

Other nations including Australia, Canada and the EU are also trying to wean themselves off a heavy dependency on Chinese metals with plans that include investing in domestic mining or stockpiling material.

Thursday’s analysis drew on geologic data from the US, Australian and Canadian Geological Surveys, among other sources. 

Rare earth elements, which are essential for the production of magnets, have drawn particular attention in recent months following a temporary Chinese export ban on the materials that upended the global supply chain.

Despite their name, these metals are not especially rare but are often not economic to extract, with many mined as byproducts of other minerals. 

The amount of critical minerals that currently end up as US mining waste could “exceed US imports and US manufacturing demand for most elements,” the researchers said.

For 15 elements — including rare earths, gallium and germanium — recovering less than 1 per cent of the potential byproducts found in mines across the US would be enough to replace imports, they found.

For another 11, including the battery metal lithium, recovery of between 1 and 10 per cent would be needed to replace imports, they said.

“US metal mines already have sufficient mineral endowment to substantially reduce the nation’s mineral [deficit],” they said. “Unrecovered, these byproducts contribute to the country’s growing industrial waste.”

Walmart’s second-quarter results are showing that United States consumers across the spectrum are still flocking to the retailer’s stores despite economic headwinds, but its shares have dipped as the company’s margins ebbed and inventory costs rose.

The world’s largest retailer has scooped up market share from rivals as wealthier consumers frequent the store more often, worried about the effects of tariffs on prices, the company’s results on Thursday showed.

That has fueled an 85 percent surge in the stock over the last year-and-a-half that some analysts say has made its valuation too lofty.

Shares were down 4 percent in midday trading in New York, as its second-quarter profit was lower than expected, registering Walmart’s first earnings miss in more than three years.

Investors also focused on Walmart’s gross margins for the quarter, which fell short of their expectations, even though the company raised its fiscal year sales and profit forecasts.

Overall gross margins were about flat at 24.5 percent versus 24.4 percent last quarter, missing consensus estimates of 24.9 percent, according to brokerage DA Davidson.

“Expectations were high for a margin beat and we didn’t get that, so we’re getting a little bit of a pullback on the stock,” said Steven Shemesh, RBC Capital Markets analyst.

Still, the Bentonville, Arkansas-based chain’s results showed it has continued to benefit from growing price sensitivity among Americans, earning revenue of $177.4bn in the second quarter. Analysts on average were expecting $176.16bn, according to LSEG data. Adjusted earnings per share of 68 cents in the second quarter fell short of analyst expectations of 74 cents.

Consumer sentiment has weakened due to fears of tariffs fueling higher inflation, hitting the bottom lines of some retail chains, but Walmart’s sales have remained resilient. Companies have been able to withstand paying those import levies through front-running of inventories, but as those products are sold, the next shipments are pricier, Walmart CEO Doug McMillon said.

“As we replenish inventory at post-tariff price levels, we’ve continued to see our cost increase each week,” he said on a call with analysts, noting those costs will continue rising in the second half of the year. The effects of tariffs have so been gradual enough for consumer habits to change only modestly.

Walmart had warned it would increase prices this summer to offset tariff-related costs on certain goods imported to the US, a move that drew criticism from President Donald Trump. Consumer-level inflation is increasing modestly, while wholesale inflation spiked in July to its fastest rate in more than three years.

According to an S&P Global survey released on Thursday, input prices paid by businesses hit a three-month high in July, with companies citing tariffs as the key driver. Prices charged by businesses for goods and services hit a three-year high, as companies passed along costs to consumers. A day earlier, rival Target warned of tariff-induced cost pressures.

Walmart got a boost from a sharper online strategy as more customers relied on home deliveries. Its global e-commerce sales jumped 25 percent during the second quarter, and Walmart said one-third of deliveries from stores took three hours or less.

Shoppers adjust to higher prices

McMillon expects current shopping habits to persist through the third and fourth quarters. He noted middle- and lower-income households are making noticeable adjustments in response to rising prices, either by reducing the number of items in their baskets or by opting for private-label brands. This shift has not been seen among higher-income households, which Walmart defines as those earning over $100,000 annually.

Walmart expects annual sales to grow in the range of 3.75 percent to 4.75 percent, compared to its prior forecast of a 3 percent to 4 percent increase. Adjusted earnings per share are expected in the range of $2.52 to $2.62, compared to its previous range of $2.50 to $2.60.

Chief Financial Officer John David Rainey said the company is looking at more possible financial outcomes than before because of trade policy talks, uncertain demand, and the need to stay flexible for future growth. Based on what it saw in the second quarter, Walmart expects the impact on margins and earnings from the higher cost of goods to be smaller in the current quarter than it previously thought, Rainey said.

“Broad consumer and macro trends remain favourable to Walmart, especially in the shape of consumers wanting to maximise bang for their buck,” said Neil Saunders, managing director of retail consultancy GlobalData.

Walmart’s total US comparable sales rose 4.6 percent, beating analysts’ estimates of a 3.8 percent increase. The company noted strong customer response to over 7,400 “rollbacks,” its term for discounted prices, with 30 percent more rollbacks on grocery items.

Average spending at the till rose 3.1 percent from an increase of 0.6 percent last year, but growth in customer visits fell to 1.5 percent from 3.6 percent in the year-earlier period. Walmart logged 40 percent growth in marketplace sales, including electronics, automotive, toys, and media and gaming.

Two-thirds of what Walmart sells in the US is domestically sourced, executives had said last quarter, which gave it some insulation from tariffs compared to competitors.

This is how, in retail-land, to shatter your credibility with investors in one short statement: confess to a significant overstatement of profits related to the recognition of payments from suppliers.

This stuff is both sensitive – witness the upheaval after an episode at Tesco a decade ago – and basic. While it is normal for retailers to receive payments from suppliers related to the volume of goods sold, or promotional activity, accounting rules are strict. The sums must be booked as they are earned. In a multi-year agreement, payments cannot all be taken upfront.

WH Smith’s last annual report was also clear that the principle should be straightforward to put into practice: “The level of complexity and judgment is low in relation to establishing the accounting entries and estimates, and the timing of recognition.”

Thus a £30m profits overstatement in WH Smith’s North American division – “largely due to the accelerated recognition of supplier income” – is enormous in the context of the size of the operation. The estimate of headline trading profits in the unit this year has been cut from £55m to £25m.

Group-wide profits should still arrive at £110m this year because the UK operation – think shiny shops in airports and railway stations, rather than the now-sold dusty high street stores – is still bigger. But the 42% fall in the group’s share price on Thursday, equating to almost £600m in terms of stock-market value, still looks more than justified.

North America was meant to be the gleaming growth opportunity for WH Smith. The promise, after the sale of its UK high street shops, was for a pure “global travel” retailer with a single-minded focus on expanding its presence. Its US business takes in a tech and gadget format, InMotion, plus stores for other retailers. About 40 shops were opened in US airports last year on the way to making the division “an increasingly significant part of the group”, as Carl Cowling, the chief executive, put it.

At least for now, the expansion plans are intact and it’s just a question of correcting the accounting errors and waiting for Deloitte, a freshly appointed independent reviewer, to run a forensic check on all the supplier contracts. Well, let’s see. These types of accounting cock-ups rarely become smaller on closer inspection and the affair raises questions that Cowling, the chair, Annette Court, and the board haven’t begun to address.

For starters, WH Smith investors will want a comprehensive account of how the financial controls could have failed so badly that more than half this year’s promised profits from the US could evaporate in one swoop. Then they will want to know the degree to which the US operation is dependent on supplier payments. What would returns look like without them? As Peel Hunt’s analyst said: “Bigger questions remain about the margin structure of the US businesses.”

Come back in November for WH Smith’s full-year numbers and its complete version of what went wrong. Until then, the shares – now at the lowest in a decade – look like dead money. The US rollout plan requires projections shareholders can believe.

A Russian state-backed messenger application called Max, a rival to WhatsApp that critics say could be used to track users, must be pre-installed on all mobile phones and tablets bought in the country starting next month, the Russian government said on Thursday.

The decision to promote Max comes as Moscow, locked in a standoff with the west over Ukraine, is seeking greater control over the internet. The Kremlin said in a statement that Max, which will be integrated with government services, would be on a list of mandatory pre-installed apps on all “gadgets”, including mobile phones and tablets, sold in Russia from 1 September. The firm behind Max said this week that 18 million users had downloaded its app, parts of which are still in a testing phase.

State media says accusations from Kremlin critics that Max is a spying app are false and that it has fewer permissions to access user data than rivals WhatsApp and Telegram.

It will also be mandatory from 1 September for Russia’s domestic app store, RuStore, which is pre-installed on all Android devices, to be pre-installed on Apple devices. A Russian-language TV app called Lime HD TV, which allows people to watch state TV channels free of charge, will be pre-installed on all smart TVs sold in Russia from 1 January.

The push to promote homegrown apps comes after Russia said this month it had started restricting some calls on WhatsApp, owned by Meta Platforms, and on Telegram, accusing the foreign-owned platforms of failing to share information with law enforcement in fraud and terrorism cases.

WhatsApp, which in July had a reach of 97.3 million users in Russia, responded by accusing Moscow of trying to block Russians from accessing secure communications, while Telegram, which had a reach of 90.8 million users, said it actively combats the harmful use of its platform.

The third most popular messenger app in July, according to Mediascope data, was VK Messenger, at 17.9 million users, an offering from the same state-controlled tech company VK which developed Max.

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Russia’s interior ministry said on Wednesday that Max was safer than foreign rivals, but that it had arrested a suspect in the first fraud case using the new messenger.

BankIslami, one of Pakistan’s fastest-growing Islamic financial institutions, reported a profit before tax (PBT) of PKR 8.95 billion for the first half of 2025 and announced an interim dividend of PKR 1.50 per share (15%) as it continues to transform into a digital and regionally competitive institution.

BankIslami’s Non-Funded income surged by over 90%, despite declining policy rates and compressed spreads. While total income contracted by 4.9%, the decline was modest compared with industry trends. Operating expenses rose 47%, reflecting strategic investments in branch network expansion, digital infrastructure, and the acquisition of the 32-storey tower in Karachi, set to become the bank’s new headquarters.

Deposits grew by 12.7%, driven by a 37.9% increase in current accounts, pushing the CASA ratio to a record 70%. The Capital Adequacy Ratio stood at 19.37%, comfortably above regulatory requirements, while the Asset-to-Deposit Ratio remained healthy at 43.3%. Delinquent financing declined by 8% to PKR 22.3 billion, though the infection ratio inched up from 7.4 to 8.2% due to a smaller financing base.

The Bank’s commitment to Riba-free banking earned global recognition in the period under review. BankIslami was named Pakistan’s Best Islamic Bank by Euromoney and received the Pakistan Digital Award for Best Social Media Campaign for its “Saving Humanity from Riba” initiative.

Commenting on BankIslami’s performance, President & CEO, Rizwan Ata, commented: “BankIslami’s performance in the first half shows that we are ready to take on challenges and continue meeting the expectations of our customers. What drives us forward is not only our growth aspirations but our mission of Saving Humanity from Riba. Our teams have shown resilience in challenging times, and as we move ahead, we will stay true to our purpose and remain firm on our journey.”

Earlier this year, BankIslami launched aik – Pakistan’s first Islamic Digital Banking experience. This initiative is poised to lead the way in the digital transformation of Islamic finance by establishing a dedicated, fully digital division offering Riba-free financial products for a modern, tech-savvy clientele.

BankIslami currently operates over 550 branches and offers a comprehensive suite of Shariah-compliant banking products to its customers.

The Bank continues to strengthen its presence across high-impact areas, including Digital Banking, Cash Management, Investment Banking, Trade, and Home Remittance, further enhancing customer experience and service delivery. It remains focused on executing its strategy of sustainable growth through prudent financial management and customer-centric innovation.