Sacituzumab govitecan-hziy

Before the ASCO presentation, BMS already pushed iza-bren into global testing as a first-line treatment for PD-L1-ineligible triple-negative breast cancer patients.\n A first-in-class bispecific antibody-drug conjugate that Bristol Myers Squibb paid $800 million for has shown strong phase 3 results from China that suggest it could put up a fight against blockbuster TROP2 agents in triple-negative breast cancer (TNBC).The candidate, an EGFRxHER3 ADC called izalontamab brengitecan (iza-bren), significantly reduced the risk of death by 40% compared with the physician’s choice of chemotherapy in previously treated TNBC, according to data set to be shared at the 2026 American Society of Clinical Oncology annual meeting.In the China-only study conducted by BMS’ Chinese partner Sichuan Biokin Pharmaceutical, patients who took iza-bren lived a median 15.9 months, versus 12.5 months in the control arm.Iza-bren also significantly improved progression-free survival by 71%, as patients who took the ADC went a median of 8.5 months without progression, compared to 3.1 months with chemo. “This is a very important drug,” Cristian Massacesi, M.D., chief medical officer of BMS, said in an interview with Fierce, pointing to its potential across multiple tumor types. Besides the TNBC result, another China phase 3 study—presented at ASCO—found that iza-bren significantly lowered the risk of death by 36% versus chemotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma following first-line treatment with a PD-1/L1 inhibitor plus platinum-based chemotherapy. Iza-bren prolonged median overall survival by 2.7 months to 9.8 months.For TNBC, BMS has already pushed iza-bren into global testing as a first-line treatment for PD-L1-ineligible patients. If approved, the EGFRxHER3 med will need to compete against established TROP2-directed ADCs, one of which, AstraZeneca and Daiichi Sankyo’s Datroway, was recently approved in the same first-line setting. Gilead Sciences’ blockbuster Trodelvy is not far behind, with an FDA decision expected in July for its potential use in patients regardless of PD-L1 eligibility.In its own global second-line study, called Ascent, Trodelvy beat chemo by 49% on overall survival. The Gilead drug extended median overall survival to 11.8 months, versus 6.9 months in the control group.Launched in September 2025—a few months after Trodelvy’s dual positive readouts in first-line TNBC—BMS’ IzaBright-Breast01 trial still intends to use chemo as the comparator. The phase 2/3 study is currently in its phase 2 dose characterization stage. Before iza-bren’s TNBC readout at ASCO, two experts pointed out “long-term challenges with the feasibility of enrolling topo1i-ADC trials without head-to-head comparisons,” Leerink analysts mentioned in a May 27 note. Iza-bren, Trodelvy and Datroway all use topo1 inhibitors as their payloads. For the Leerink team, these market dynamics give Trodelvy and Datroway a “significant first-mover advantage” in first-line TNBC.Two other phase 2/3 studies are separately evaluating iza-bren in immunotherapy-pretreated bladder cancer and EGFR inhibitor-pretreated EGFR-mutated non-small cell lung cancer (NSCLC), respectively.In lung cancer, iza-bren may again have to square off with a TROP2 ADC. AZ and Daiichi’s Tropion-Lung15 trial is testing Datroway, with or without Tagrisso, in post-Tagrisso EGFR-mutant NSCLC. The study is expected to read out in the second half of 2026.Meanwhile, Massacesi is already looking beyond BMS’ existing pivotal programs.“The question will be more on how we continue to build iza-bren in combination, probably with pumitamig,” Massacesi said, referring to BMS’ BioNTech-partnered PD-L1xVEGF bispecific. “This is where I foresee the biggest benefit, and where I definitely will have a study that we will compare versus the standard of care that can be inclusive also of other ADCs.” For its upcoming competition with TROP2 ADCs, BMS’ chief commercialization officer, Adam Lenkowsky, expressed optimism in iza-bren’s potential combinability in the context of the side effect interstitial lung disease (ILD). ADCs are associated with an increased risk of pulmonary adverse events, such as ILDs, which have been more notably observed with Daiichi’s DXd platform.In the China TNBC trial, all-grade ILD was reported in 1.4% of patients in the iza-bren arm, versus zero in the control group. This low grade of ILD could play out nicely in lung cancer patients, who may be more prone to the side effect.Overall, some of the most common grade 3 or above treatment-emergent adverse events between iza-bren and chemo were neutrophil count decreased (58.0% vs. 46.8%), white blood cell count decreased (56.0% vs. 33.2%), platelet count decreased (52.7% vs. 2.4%), and anemia (46.9% vs. 3.9%).

As it awaits an FDA decision on the use of Trodelvy (sacituzumab govitecan) to treat certain patients with first-line triple-negative breast cancer (TNBC), Gilead Sciences on Tuesday shared data for an exploratory endpoint the FDA recently criticised. Last year, the drugmaker claimed success in the Phase III ASCENT-04/KEYNOTE-D19 study, which is comparing a combination of its TROP2-directed antibody-drug conjugate (ADC) with Merck & Co.'s Keytruda (pembrolizumab) against the PD-1 inhibitor plus chemotherapy in patients with newly diagnosed, PD-L1–positive, inoperable, locally advanced or metastatic TNBC.At the 2025 American Society of Clinical Oncology (ASCO) meeting, Gilead reported that in the  443-patient study, the ADC-mAb duo significantly extended progression-free survival (PFS) to 11.2 months versus 7.8 months for standard of care. Trodelvy plus Keytruda cut the risk of disease progression or death by 35%.The combo is now under review with the FDA; Trodelvy is currently approved for second-line or later metastatic TNBC and for certain patients with pre-treated HR-positive/HER2-negative metastatic breast cancer.Proving PFS2's mettle?Now, at this year's ASCO conference, Gilead is detailing findings from patients who were given a second-line treatment after disease progression. The endpoint, called PFS2, measures the time from randomisation to first documented progression on next-line therapy or death due to any cause, whichever occurred first. Of the 170 patients in the control group who progressed, 119 opted to receive a subsequent treatment, and 81% were given second-line Trodelvy monotherapy; 125 patients who were initially randomised to the Trodelvy-Keytruda regimen saw their disease progress, and 69 chose to take a second-line treatment, mainly receiving taxanes, platinum chemotherapy or capecitabine.  Gilead reported that PFS2 was improved in the Trodelvy-Keytruda group compared with the Keytruda-chemo arm, despite the high rate of crossover. The median time to second subsequent therapy was 21 months for those who started in the comparator cohort, and has not yet been reached in the experimental group (hazard ratio of 0.67).Speaking to media ahead of the presentation, study investigator Kevin Kalinsky said the data "demonstrate an improved clinical benefit in those patients randomly assigned to front-line [Trodelvy and Keytruda]," with the regimen leading to a 33% reduction in risk of a PFS2 event. Regulatory discordanceKalinsky also acknowledged that PFS2 "has been a really hot topic" with the FDA recently, highlighting a decision from the agency's Oncologic Drugs Advisory Committee (ODAC) not to support AstraZeneca's oral selective oestrogen receptor degrader (SERD) camizestrant in treating certain patients with breast cancer. The FDA has since asked AstraZeneca for additional analyses linked to longer-term efficacy outcomes, while, in contrast, the EMA's drug advisory panel recently backed approval of camizestrant in the EU based on the same data."There's a bit of a discordance right now between FDA not recognising PFS2 as a regulatory endpoint, though EMA uses it as a supportive endpoint, not an endpoint on its own," Kalinsky said. "But PFS2 can be used to measure long-term clinical benefit when overall survival data are immature, and is particularly valuable when overall survival can be confounded by crossover."Eleonora Teplinsky, an ASCO expert on breast cancer asked to speak to ASCENT-04/KEYNOTE-D19's findings, seemed to agree with the value of the PFS2 results. "I think this study is really important and further supports…[Trodelvy plus Keytruda] becoming a new standard of care for PD-L1–positive, untreated, advanced triple-negative breast cancer," Teplinsky said, adding that the study's importance stems from the fact that "a significant amount of patients are not able to receive subsequent lines of therapy for metastatic triple-negative breast cancer. And this PFS2 analysis really supports the long-term clinical benefit and shows us that what we were giving in the first-line really makes a difference toward sustained benefit in subsequent lines of therapy.""I think this is critically important and hopefully will provide a new standard of care for our patients," she concluded.