Category: 3. Business

The development program for the immunotherapy KB707 will prioritize an inhaled formulation of the agent for the treatment of patients with non–small cell lung cancer (NSCLC), according to an announcement from Krystal Biotech.¹

As such, the company announced it was also pausing enrollment of the phase 1/2 OPAL-1 trial (NCT05970497) evaluating intratumoral KB707 in patients with locally advanced or metastatic solid tumor malignancies.

The company was also granted an end of phase 2 meeting with the FDA in October 2025 to further discuss developmental pathways for inhaled KB707.

“The acceleration of our work on inhaled KB707 is a reflection of both the clear and acute unmet need that exists for new treatments of NSCLC and the promising efficacy profile we have observed to date with inhaled KB707,” Suma Krishnan, president of Research and Development of Krystal Biotech, stated in a news release. “We look forward to meeting with the FDA and bringing another urgently needed therapeutic option to patients.”

Data from the phase 1/2 KYANITE-1 trial (NCT06228326) presented at the 2025 ASCO Annual Meeting showed that efficacy-evaluable patients with NSCLC treated with inhaled KB707 (n = 11) achieved an overall response rate (ORR) of 27% as of the abstract data cutoff; patients experienced partial response (PR; n = 3), stable disease (n = 5), or progressive disease (n = 3).² With extended follow-up, the ORR was 36%, with 4 patients achieving a PR.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) were reported in 66.7% of patients, although no grade 4 or 5 TRAEs occurred. The most common any-grade TRAEs comprised chills (25.6%), cytokine release syndrome (CRS; 23.1%), fatigue (20.5%), flu-like illness (15.4%), dyspnea (15.4%), vomiting (12.8%), and pyrexia (10.3%). Notably, the rate of grade 3 CRS was 2.6%.

KB707 Background and KYANITE-1 Overview

The novel gene therapy KB707 is a replication-defective herpes simplex virus type 1–based vector encoding human interleukin (IL)-12 and IL-2. The agent is intended to bring high cytokine doses to the local tumor microenvironment.

In the open-label, dose-escalation and -expansion KYANITE-1 study, investigators enrolled patients with at least 1 measurable lung lesion and a histologically confirmed solid tumor malignancy of the lungs to participate in the KB707 monotherapy portion of the study.

The trial is also enrolling patients with histologically or cytologically confirmed stage III/IV NSCLC to receive KB707 in combination with pembrolizumab (Keytruda) with or without chemotherapy. Notably, eligible patients from the monotherapy cohorts are allowed to roll over to participate in the combination cohorts.

During the monotherapy phase, KB707 was administered at doses ranging from 10⁸ to 10⁹ plaque-forming units (PFU; n = 16). During dose expansion (n = 23), patients received the agent at 10⁹ PFU. The agent was administered on days 1, 8, 15, 36+, and 57+, with tumor evaluation also performed on day 57 or beyond.

Safety, immunologic biomarkers, and preliminary efficacy were the primary objectives for the monotherapy portion of the study.

In the efficacy-evaluable cohort, the median age was 71 years (range, 54-77), and most patients were female (63.6%), had an ECOG performance status of 1 (90.9%), and had stage IV disease (100%). Additionally, 18.2% of patients had a PD-L1 expression of at least 1%, and 45.5% of patients had PD-L1 expression under 1%; PD-L1 status was unknown in 36.4% of patients.

Patients had received a median of 4 prior lines of therapy. Notably, 63.6% of patients had undergone 1 prior line of immunotherapy, and 36.4% of patients had received at least 2 prior lines of immunotherapy.

References

1. Krystal Biotech announces update on development plans for oncology program KB707 and prioritization of inhaled KB707 for the treatment of non-small cell lung cancer. News release. Krystal Biotech. August 21, 2025. Accessed August 22, 2025. https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-update-development-plans-oncology
2. Ma WW, McKean M, Villaruz L, et al. Inhaled KB707, a novel HSV-based immunotherapy, as a monotherapy in patients with advanced solid tumor malignancies affecting the lungs: Efficacy and safety results from a phase 1/2 study. J Clin Oncol. 2025;43(suppl 16):2575. doi:10.1200/JCO.2025.43.16_suppl.2575

A British Airways flight attendant was found high on drugs and completely naked in an onboard toilet during a flight from California to London, a court heard.

Haden Pentecost, who was described as agitated, sweating and babbling, had to be stood down by the flight’s manager when he failed to help with any pre-flight safety checks.

After complaining of stomach cramps and saying he needed to change his clothes, the attendant locked himself in one of the plane’s toilets.

A colleague found him there naked and oblivious to the fact he had no clothes on. She had to dress him before moving him into a free seat, the court was told.

The flight attendant was spoken to by the captain before a health professional was called, the magistrate was told.

The court heard Pentecost had dilated pupils, a high heart rate, and had to be checked every 20 minutes until the plane arrived at Heathrow, where paramedics took him to hospital. A blood test later revealed he had methamphetamine and amphetamine in his system.

He has since been sacked by British Airways, the court was told.

Pentecost appeared at Uxbridge magistrates court on Friday, where he pleaded guilty to performing an aviation function while impaired by drugs. The 41-year-old from Basingstoke was granted bail to be sentenced at Isleworth crown court at a later date.

British Airways has been approached for comment.

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By Aditya Kalra and Aftab Ahmed

NEW DELHI (Reuters) -Amazon is lobbying the Indian government to ease its foreign investment rules to allow the U.S. company to buy products directly from Indian sellers to sell in overseas markets, four people with direct knowledge of the matter said.

India currently prohibits companies like Amazon and Walmart from stocking and selling goods directly to consumers, allowing them only to operate an e-commerce marketplace to connect buyers and sellers for a fee. The restrictions, which aim to protect small retailers, also apply to exports.

Amazon executives asked the Indian Commerce Ministry in a meeting on Thursday to exempt exports from the policy – which would allow Amazon India to buy the goods itself from sellers to sell to international customers, the four sources said.

The policy restrictions that Amazon and Walmart face have for years been a sore point between New Delhi and Washington, which are also currently struggling to strike a trade deal.

Three industry groups backing small retailers opposed any more easing of restrictions for Amazon and Walmart’s Flipkart – which also attended the meeting, the sources added.

The retailer groups reiterated their long-standing concerns that Amazon and Flipkart have hurt small Indian retailers for years by favouring select big sellers online, and offering discounts, which hurt smaller businesses.

The U.S. companies have always maintained they comply with Indian laws. On Friday, Amazon India and Flipkart did not respond to Reuters queries.

India’s Commerce Ministry did not immediately respond to Reuters queries.

Amazon said in December it helped to generate $13 billion in cumulative exports for sellers from India since 2015, and plans to take that to $80 billion in total by 2030.

Amazon and Flipkart are leading players in India’s e-commerce market, which was estimated to be worth $125 billion in 2024 and is set to top $345 billion by 2030, according to India Brand Equity Foundation.

Amazon said during Thursday’s meeting that exempting exports from the rules would benefit small sellers as the company could help to facilitate customs clearance processes, giving sellers greater access to international markets, three of the sources said.

“It was a heated meeting … the small traders and their supporters opposed it saying they wanted no concession for foreign e-commerce players,” said one of the four sources, who attended the meeting.

The internal government agenda of the meeting, seen by Reuters, shows New Delhi has not yet reached a decision.

The document said the government wants to ensure that any changes to the policy to exempt exports will not allow foreign e-commerce companies to “engage in direct sale of listed goods/products to Indian consumers”, which would hit small retailers.

Any changes to the policy should “ensure sufficient demarcation between the goods/products meant only for exports and other … meant for sale to Indian consumers,” the government document said.

(Reporting by Aditya Kalra and Aftab Ahmed. Editing by Jane Merriman)

Health Canada has approved glofitamab (Columvi) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified who are not candidates for autologous stem cell transplant (ASCT).¹

The decision makes glofitamab the first bispecific antibody regimen available in Canada for patients with DLBCL whose disease has returned or has not responded to initial therapy. The approval is supported by findings from the phase 3 STARGLO trial (NCT04408638), in which glofitamab plus GemOx generated significant improvements in overall survival (OS) compared with rituximab (Rituxan) plus GemOx.

“DLBCL is an aggressive and life-threatening form of lymphoma, leaving many patients in urgent need of additional treatment options,” Antonella Rizza, chief executive officer of Lymphoma Canada, stated in a news release. “The availability of novel therapies has the potential to address critical gaps in care and offer new possibilities for patients who face relapse or have limited options.”

Previously Reported FDA Status of Glofitamab in DLBCL

Notably, in July 2025, the FDA issued a complete response letter (CRL)to the supplemental biologics license application seeking the approval of glofitamab-gxbm plus GemOx for the treatment of patients with relapsed/refractory DLBCL who have received 1 or more prior lines of therapy and are not eligible to undergo ASCT.² The CRL noted that the STARGLO data were not sufficient to support the regimen’s approval for the United States population.

Efficacy and Safety Data From the STARGLO Study

At the primary analysis, with a median follow-up of 11.3 months, patients who received glofitamab plus GemOx achieved a 41% reduction in the risk of death compared with those treated with rituximab (Rituxan) plus GemOx (HR, 0.59; 95% CI, 0.40-0.89; P = .011). Furthermore, at an updated analysis, at a median follow-up of 20.7 months, the median OS was 25.5 months with the glofitamab combination vs 12.9 months with rituximab plus GemOx (HR, 0.62; 95% CI, 0.43-0.88).

Outcomes with key secondary end points also favored the glofitamab regimen. Patients who received glofitamab plus GemOx achieved a 63% reduction in the risk of progression or death (HR, 0.37; 95% CI, 0.25-0.55; P < .001).

Additionally, updated data from STARGLO presented at the 2025 ASCO Annual Meeting showed an overall response rate of 68.3% (95% CI, 61.0%-75.0%) in the glofitamab arm vs 40.7% (95% CI, 30.5%-51.5%) in the rituximab arm.³Complete responses (CRs) were observed in 58.5% (95% CI, 51.0%-65.7%) of patients treated with glofitamab plus GemOx vs 25.3% (95% CI, 16.8%-35.5%) of patients treated with rituximab plus GemOx (difference, 33.2%; 95% CI, 20.9%-45.5%).^1,3 Among complete responders in the glofitamab arm, the median duration of CR was not evaluable (NE; 95% CI, 27.2 months-NE), and at data cutoff, 42.1% of patients remained in CR.³ These respective values were 24.4 months (95% CI, 6.9-NE) and 17.6% in the rituximab arm.

Updated survival data showed that at a median follow-up of 24.7 months, the median OS in the glofitamab arm was NE (95% CI, 19.2-NE) compared with 13.5 months (95% CI, 7.9-18.5) in the rituximab arm (HR, 0.60; 95% CI, 0.42-0.85; P = .003). The 24-month OS rates were 54.4% and 33.6% in these respective arms. The median progression-free survival was 13.8 months (95% CI, 8.8-30.0) with the glofitamab regimen vs 3.6 months (95% CI, 2.5-7.1) with the rituximab regimen.

The safety profile of glofitamab plus GemOx was consistent with that of the individual agents, and no unexpected adverse effects were reported.¹

References

1. Health Canada approves Roche’s Columvi (glofitamab) as the first bispecific antibody in Canada for relapsed or refractory diffuse large B-cell lymphoma after initial therapy. News release. Roche Canada. August 21, 2025. Accessed August 21, 2025. https://www.rochecanada.com/media/health-canada-approves-roche-s-columvi-glofitamab-as-the-first-bispecific-antibody-in-canada-for-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-after-initial-therapy
2. Genentech provides update on supplemental biologics license application for Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. July 18, 2025. Accessed August 22, 2025. https://www.businesswire.com/news/home/20250718250985/en/Genentech-Provides-Update-on-Supplemental-Biologics-License-Application-for-Columvi-Combination-for-People-With-Relapsed-or-Refractory-Diffuse-Large-B-cell-Lymphoma
3. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. J Clin Oncol. 2025;43(suppl 16):7015. doi:10.1200/JCO.2025.43.16_suppl.7015

Saudi Arabia exported less Crude Oil in June despite a significant increase in Oil production, according to data from the Joint Organizations Data Initiative (JODI), Commerzbank’s commodity analyst Carsten Fritsch notes.

Additional Oil produced remaines in the domestic market

“Crude Oil exports fell by 50,000 barrels per day compared to the previous month to 6.14 million barrels per day. Oil production, on the other hand, rose by 570,000 to 9.75 million barrels per day.”

“This confirms previous statements from Saudi Arabia that the significant increase in Oil production has not led to a higher Oil supply on the world market. Instead, the additional Oil produced remained in the domestic market. Most of it is likely to have gone into storage.”

“This is because domestic Crude Oil processing fell slightly to 2.7 million barrels per day, while demand for power generation rose by 185,000 to 674,000 barrels per day. It cannot therefore be ruled out that the Oil in storage will enter the market at a later date.”

Methods to accurately predict which patients are the most likely to benefit from therapy can be elusive, according to Joyce O’Shaughnessy, MD. However, updated findings have indicated that the MammaPrint and BluePrint genomic tests could offer a predictive testing approach to elucidate which patients with hormone receptor (HR)–positive, HER2-negative early-stage breast cancer should receive adjuvant and/or neoadju- vant chemotherapy.

MammaPrint is a 70-gene assay that analyzes the most important genes associated with breast cancer recurrence.¹ The MammaPrint index classifies patients as being at high risk 2 (H2; range, –1.000 to –0.570), high risk 1 (H1; range, –0.569-0.000), low risk (range, 0.001-0.355), or ultralow risk (range, 0.356-1.000) for disease recurrence.1 BluePrint is an 80-gene test that classifies patients into luminal (further strati- fied using MammaPrint into luminal A-type [low risk] and luminal B-type [high risk]), HER2, or basal subtypes, providing insights into their long-term prognosis and potential response to systemic treatment.²

“In patients with HR-positive, HER2-negative early breast cancer, the first question is, ‘Who needs chemotherapy at all?’” O’Shaughnessy said in an interview with OncologyLive. “[Most] patients will receive endocrine therapy, and if they have high enough risk disease, they will receive a CDK4/6 inhibitor. Patients with a low 21-gene recurrence score don’t benefit from chemotherapy. We know that the MammaPrint [test] is prognostic due to data from the [phase 3] MINDACT trial [NCT00433589], but we did not [previously] have data [that] indicated that a high-risk MammaPrint score predicts bene- fit from chemotherapy or that a low-risk score predicts a lack of benefit.”

O’Shaughnessy is the Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center and the director of the Breast Cancer Research Program at Texas Oncology, US Oncology in Dallas, Texas.

MammaPrint and BluePrint Show Predictive Value

To further understand the predictive value of the tests on patient outcomes, investigators initiated the prospective, observational FLEX regis-
try study (NCT03053193).3 FLEX enrolled adult patients with stage I to III breast cancer who were eligible to receive chemotherapy and endo- crine therapy and MammaPrint, with or without BluePrint testing, in any clinical setting. The study excluded patients with metastatic, recur- rent, or stage 0 disease.

During the 2024 San Antonio Breast Cancer Symposium (SABCS), O’Shaughnessy presented data from an analysis of FLEX that demonstrated that MammaPrint and BluePrint were able to predict sensitivity to neoadjuvant chemotherapy in patients with HR-positive, HER2-negative early breast cancer.

Patients with H2 luminal and basal disease (n = 159) achieved a patholog- ical response rate of 32.7%, with a pathological complete response (pCR) rate of 28.3%. Those with H2 luminal B-type (n = 70) or H2 basal (n = 83) disease experienced pathological response rates of 21.4% and 43.4%, respectively, with respective pCR rates of 15.7% and 39.8%. Comparatively, patients with low-risk luminal A-type disease (n = 44) experienced a patho- logical response rate of 4.5%, and those with H1 luminal B-type disease (n = 242) experienced a pathological response rate of 9.5%, with a pCR rate of 7.4%.

Data from a multivariate analysis also revealed that a MammaPrint H2 classi- fication was significantly associated with a pathological response compared with H1 status (OR, 3.33; 95% CI, 1.51-7.61; P = .003).⁴

Additional data from FLEX also presented during SABCS showed that patients with a higher-risk MammaPrint score who received adjuvant chemotherapy plus endocrine therapy (n = 501) had a significantly lower risk of 5-year distant recurrence or breast cancer–specific death (hereafter, DRFI) compared with those who received endocrine therapy alone (n = 501). Patients with an ultralow MammaPrint score who received endocrine therapy experienced a 1.0% (95% CI, 0.6%-2.2%) average 5-year DRFI risk vs 0.4% (95% CI, 0.1%-1.0%) among those who received chemotherapy plus endocrine therapy. Among patients with a low score, these respective rates were 3.2% (95% CI, 2.2%-4.5%) and 1.5% (95% CI, 1.0%-2.1%).⁵

Notably, patients in the H1 group who received endocrine therapy alone experienced an average 5-year DRFI risk of 10.0% (95% CI, 5.6%-14.6%) compared with 4.4% (95% CI, 2.6%-6.4%) among patients who received endocrine therapy plus chemotherapy, for a risk difference of 5.6% (95% CI, 3.0%-8.2%). In the H2 risk group, these rates were 19.1% (95% CI, 14.8%-24.8%) vs 8.2% (95% CI, 6.5%-10.6%), respectively, representing a risk difference of 10.9% (95% CI, 8.3%-14.2%).⁵

“These are the first data using MammaPrint showing that the higher the risk [score], the greater the benefit from chemotherapy,” O’Shaughnessy noted. “We’ve been giving chemotherapy to those women anyway because we know they have a poor prognosis, but this is the first time we’ve seen level 1, prospective, predictive data. The caveat here is that this is not a randomized trial. This [study] has a large database of real-world evidence, but the deci- sion to give chemotherapy or not is made by the physician and patient.”

Findings from FLEX have also shown the capability of MammaPrint and BluePrint to help inform the need for the addition of an anth- racycline to chemotherapy.

During the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, O’Shaughnessy presented data from FLEX that demonstrated that patients with H1 luminal disease who received an anthracy- cline plus a taxane (n = 184) achieved a 3-year relapse-free survival (RFS) rate of 95.3% (95% CI, 91.8%-98.8%) compared with 97.1% (95%, 95.1%- 99.2%) among those who received a taxane plus cyclophosphamide (n = 346). However, patients with luminal H2 tumors who received an anth- racycline plus a taxane (n = 44) experienced a 3-year RFS rate of 97.7% (95% CI, 93.4%-100%) vs 86.4% (95% CI, 74.2%-100.0%) among those who received a taxane plus cyclophos- phamide (n = 40).⁶

“Both of these tests are endorsed by National Comprehensive Cancer Network and ASCO guidelines, so I don’t believe there are any barriers [to access],” O’Shaughnessy said.

“In FLEX, MammaPrint and BluePrint are also being evaluated in [patients with] HER2-positive and triple-negative disease. There could poten- tially be some limitations on reimbursement there because it is a research trial. However, if we look at [data from] MINDACT, there were patients with triple-negative breast cancer who didn’t benefit from chemotherapy if they had a low-risk MammaPrint score. If they had a high-risk MammaPrint score, they had a worse prognosis and did benefit from chemotherapy.

In general, in the HR-positive, HER2-negative context, there are not any barriers to ordering [these tests], getting the results in a timely fash- ion, or to reimbursement.”

Breast Cancer Experts Gather at SOBO to Discuss the Latest Data

During the upcoming 23rd Annual School of Breast Oncology® (SOBO), which is hosted by Physicians’ Education Resource®, LLC (PER®), expert investigators in the field of breast cancer will gather to further discuss how molecular and genomic testing can be used to optimally select treatment approaches for individ-ual patients. O’Shaughnessy is set to serve as the chair of the event, which will also feature sessions on present and emerging imaging modalities, best practices for the locoregional management of patients with breast cancer, and the latest clinical trial data that could shape future therapeutic approaches. The program will be held from November 6 to 8, 2025, in Atlanta, Georgia.

“SOBO will be a 3-day deep dive [that will cover] new data based around case discussions [that aim to determine] how we apply these new data to practice,” O’Shaughnessy said. “I always thoroughly enjoy the data presentations but am also [looking forward to] the spirited inter- actions that occur during a moderated case and panel discussion between the reconstruc- tive surgeons, the plastic surgeons, and the radiation oncologists.”