Buoyed by a clean sweep of five positive phase 3 readouts in China, Bristol Myers Squibb’s Chief Medical Officer, Cristian Massacesi, M.D., is voicing growing confidence in the company's first-in-class bispecific antibody-drug conjugate izalontamab brengitecan (iza-bren), even as the New Jersey pharma has yet to match one China study with a global clinical program.
The latest additions to the phase 3 wins, Panku-Lung01 and Panku-Breast01, conducted by iza-bren’s original developer, Sichuan Biokin Pharmaceutical, have now had their detailed data presented at the European Society for Medical Oncology 2026 Congress in Madrid.
In Panku-Lung01, iza-bren, an EGFRxHER3 ADC, significantly reduced the risk of progression or death by 60% compared with platinum-based chemotherapy in patients with EGFR-mutant non-small cell lung cancer following progression on a third-generation EGFR tyrosine kinase inhibitor.
In Panku-Breast01, iza-bren improved progression-free survival by 59% versus physician’s choice of chemotherapy in HR-positive, HER2-negative breast cancer patients who had tried endocrine therapy, CDK4/6 inhibitors and chemo.
“This brings five out of five positive phase 3 studies with this ADC. That is quite remarkable,” Massacesi said in an interview with Fierce.
For EGFR-mutated NSCLC, BMS has already launched the phase 2/3 Izabright-Lung01 trial in the post-TKI setting, with data expected in 2028. A separate global phase 3 in the first-line setting, Izabright-Lung02, just started last month.
Massacesi described the Panku-Lung01 data as especially relevant for setting expectations around the drug’s performance in those global studies because EGFR mutations are more common in Asian patients than in Western patients.
In Panku-Lung01, patients in the iza-bren arm achieved a median PFS of 11.1 months, versus 5.7 months for control.
Overall survival data were immature but showed a favorable trend toward a 34% improvement. For a U.S. filing, a statistically significant OS is necessary, the FDA previously told Summit Therapeutics, which is seeking FDA approval for its Akeso-partnered PD-1xVEGF bispecific ivonescimab in the same second-line EGFR NSCLC indication.
Iza-bren’s results so far compare favorably to ivonescimab’s by cross-trial comparison, which should generally be interpreted with a grain of salt given differences in baseline patient characteristics and follow-up time.
In the China-only Harmoni-A trial in post-TKI EGFR NSCLC, ivonescimab plus chemo achieved a median PFS of 7.1 months, versus 4.8 months for chemo alone, translating into a risk reduction of 54%. Compared with iza-bren’s Panku-Lung01, Harmoni-A also enrolled a small group of patients who had tried earlier-generation TKIs.
Objective response rate was 50.6% in the ivonescimab combo group, compared with 35.4% in the control arm. Median duration of response (DoR) landed at 6.6 months versus 4.2 months, respectively.
In Panku-Lung01, the confirmed ORR was 60.2% for iza-bren versus 34.5% for chemo, respectively, and the median DoR was 10.5 months versus 5.7 months, respectively.
Harmoni-A eventually hit statistically significant OS at its final analysis, a claim that Panku-Lung01 can’t yet make.
As to the Panku-Breat01 study, iza-bren significantly improved median PFS to 8.2 months versus four months for chemo. Confirmed ORR was 40.5% versus 20.2%, respectively.
OS, according to Massacesi, was “very immature” and was therefore not presented.
Iza-bren’s data here again look competitive. In the global phase 3 Tropion-Breast01 trial in HR+/HER2- breast cancer patients who had tried endocrine therapy and chemo, AstraZeneca and Daiichi Sankyo’s TROP2 ADC Datroway led to a 37% PFS benefit over the same group of chemo used in Panku-Breast01. Median PFS was 6.9 months versus 4.9 months, respectively; and ORR was 36.4% versus 22.9%, respectively.
Still, BMS has not launched a global phase 3 for iza-bren to match Panku-Breast01. As Massacesi suggested, the HR+/HER2- breast cancer landscape is more complicated.
“We are assessing this opportunity,” the BMS exec said. “The data are very supportive. This is a place where there are many other treatment options and new entry, but we are assessing plans to eventually run a phase 3 study.”
Besides TROP2 ADCs, oral SERDs have emerged as a new class of treatments for certain HR+/HER2- patients, and Celcuity just got FDA approval for its PI3K/mTOR inhibitor, Revtorpyk.
Meanwhile, certain patients traditionally regarded as HER2-negative can now be treated by AZ and Daiichi’s HER2 ADC Enhertu in a new HER2-low category.
In Panku-Breast01, iza-bren showed similar PFS benefits across HER2 expression levels, including a 59% improvement in IHC 0, 47% in IHC 1+ and 68% in IHC 2+/ISH-, according to a subgroup analysis.
Now that iza-bren has consistently shown PFS benefits in the 50%-to-60% range across nasopharyngeal, esophageal, triple-negative breast cancer, HR+/HER2- breast cancer and EGFR-mutant NSCLC in its China studies, Massacesi said they give BMS confidence in its ongoing global phase 3 trials.