Izalontamab

Bristol Myers Squibb and SystImmune have announced that positive results from studies evaluating a bispecific antibody-drug conjugate (ADC) have been reported by SystImmune’s parent company. Sichuan Biokin Pharmaceutical Co (Biokin), the parent company, reported positive results from prespecified interim analyses of two phase 3 studies evaluating izalontamab brengitecan (iza-bren), an investigational and potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC). The ADC has now demonstrated clinical benefit in three phase 3 trials in China, underscoring its broad therapeutic potential in multiple tumour types. The studies demonstrated iza-bren achieved statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) in heavily pretreated, unresectable locally advanced or metastatic triple-negative breast cancer (TNBC; PANKU-Breast02) and recurrent or metastatic oesophageal squamous cell carcinoma (ESCC; PANKU-Esophagus01). The data, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, supports iza-bren’s potential as a new standard of care in these challenging cancer types. Iza-bren has now shown clinical benefit in three phase 3 trials, underscoring its broad therapeutic potential. PANKU-Breast02 is the first phase 3 study of a bispecific ADC to report positive results for dual primary endpoints of both PFS and OS in TNBC, while PANKU-Esophagus01 marks the first phase 3 trial of a bispecific ADC in oesophageal cancer to report positive dual primary endpoints of both PFS and OS. Iza-bren previously demonstrated positive phase 3 results in recurrent or metastatic nasopharyngeal carcinoma (NPC), presented at ESMO 2025. Yi Zhu, CEO of Biokin, SAID: “As a potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate, iza-bren has now shown significant clinical benefit in three phase 3 trials in different cancer types, and the strength of the data presented at ASCO further reinforces the value iza-bren can deliver over current standards of care.” Cristian Massacesi, executive vice president, chief medical officer and head of development at Bristol Myers Squibb, said: “Iza-bren can address a critical gap for patients who develop resistance or experience disease progression after prior therapies and may also hold potential in earlier lines of therapy. “We have a broad development program for iza-bren and believe it has the potential to be a cornerstone treatment in a number of different cancers and easily combined with other therapies.”

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%).