Bristol Myers Squibb and SystImmune have reported positive Phase 3 results for experimental cancer drug izalontamab brengitecan (iza-bren), which nearly doubled median progression-free survival compared with chemotherapy in patients with previously treated EGFR-mutated non-small cell lung cancer (NSCLC).

 

Results from the PANKU-Lung01 trial showed that patients receiving iza-bren achieved median progression-free survival (PFS) of 11.1 months, compared with 5.7 months among those receiving platinum-based chemotherapy. The difference was statistically significant, with a hazard ratio of 0.40.

 

The findings mark a potential advance for patients whose disease progresses after treatment with an EGFR tyrosine kinase inhibitor (TKI), a group with historically limited treatment options.

 

The randomized, multicenter Phase 3 study is the first to evaluate a dual-targeting EGFRxHER3 bispecific antibody-drug conjugate in this patient population.

 

The trial enrolled 422 patients, with 216 assigned to iza-bren and 206 to platinum-based chemotherapy. At a median PFS follow-up of 14.6 months, the experimental drug demonstrated significant improvement in the study’s primary endpoint.

 

The confirmed objective response rate was also higher with iza-bren, at 60.2%, compared with 34.5% for chemotherapy. Median duration of response reached 10.4 months in the iza-bren group, against 5.7 months in the chemotherapy arm.

 

Overall survival data, however, remain immature. An early trend toward improved overall survival was observed with iza-bren, but further follow-up will be needed to establish whether the treatment extends patients’ lives.

 

“When EGFR-mutated NSCLC progresses after an EGFR TKI therapy, patients and physicians have historically had few effective treatment options, with chemotherapy often serving as the default, though it offers limited survival benefit,” said Professor Li Zhang, Chief Lung Cancer Expert, Sun Yat-sen University Cancer Center. 

 

“The PANKU-Lung01 findings suggest that iza-bren could change the trajectory of the disease, offering patients more time before their disease worsens. These results could mark an important shift in how we approach acquired resistance in this disease to significantly improve patient outcomes.”

 

Iza-bren demonstrated a manageable safety profile, with no new safety signals reported. Treatment-related adverse events of Grade 3 or higher were predominantly hematologic and were managed with standard supportive care.

 

Only 1.9% of patients receiving iza-bren discontinued treatment because of treatment-related adverse events. Interstitial lung disease was uncommon, with two adjudicated cases (0.9%): one Grade 3 and one Grade 1.

 

“Post-progression EGFR-mutated NSCLC represents one of oncology's challenging treatment scenarios. With iza-bren, we achieved a nearly two-fold improvement in median PFS, along with a well-understood safety profile and high response rate. This demonstrates that dual-targeting EGFR and HER3 may fundamentally shift outcomes for these patients,” said Jonathan Cheng, chief medical officer, SystImmune. 

 

“These data validate our conviction that iza-bren addresses a critical unmet need and provides much-needed innovation for patients who often have limited options after TKI failure.”

 

“The PANKU-Lung01 results mark an important inflection point for iza-bren and reinforce our belief that this potentially first-in-class EGFRxHER3 bispecific ADC could, if approved, improve outcomes across the cancer treatment landscape,” said Cristian Massacesi, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. 

 

“The breadth of clinical benefit now seen across five tumor types is highly encouraging and speaks to the potential of iza-bren to address significant unmet needs in oncology. We are committed to advancing iza-bren with urgency to deliver this innovative treatment option to patients.”