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 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 4 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.