Illustration of a bispecific antibody-drug conjugate targeting EGFR and HER3 in EGFR-mutated non-small cell lung cancer
Written By: Kalyani Boharapi,
M.Pharm (RA)
Reviewed By: Pharmacally Editorial Team
SystImmune, Inc. and Bristol Myers Squibb (BMS) reported positive Phase 3 results for investigational izalontamab brengitecan (iza-bren) in patients with previously treated EGFR-mutated non-small cell lung cancer (NSCLC). In the PANKU-Lung01 study, the EGFRxHER3 bispecific antibody-drug conjugate (ADC) nearly doubled median progression-free survival (PFS) compared with platinum-based chemotherapy.
The results were reported by SystImmune’s parent company, Sichuan Biokin Pharmaceutical on October 26, 2026. The findings were scheduled for presentation as a late-breaking oral presentation at the European Society for Medical Oncology (ESMO) 2026 Congress in Madrid, Spain, and simultaneous publication in The Lancet.
PANKU-Lung01 Shows Significant PFS Improvement
PANKU-Lung01 (NCT06382116) is a randomized, multicenter Phase 3 trial evaluating iza-bren against platinum-based chemotherapy in patients with EGFR-mutated non-squamous NSCLC whose disease progressed following treatment with an EGFR tyrosine kinase inhibitor (TKI).
At a median PFS follow-up of 14.6 months, iza-bren significantly improved the primary endpoint, as assessed by blinded independent central review (BICR).
Median PFS was 11.1 months with iza-bren, compared with 5.7 months with platinum-based chemotherapy. The hazard ratio (HR) was 0.40 (95% confidence interval [CI], 0.31–0.51; p<0.0001), corresponding to a 60% lower hazard of disease progression or death relative to chemotherapy.
The efficacy analysis included 216 patients receiving iza-bren and 206 receiving platinum-based chemotherapy.
Response Rates and Overall Survival Findings
Iza-bren also improved secondary efficacy outcomes. The confirmed objective response rate (cORR), assessed by BICR, was 60.2% with iza-bren versus 34.5% with chemotherapy. Median duration of response was 10.4 months and 5.7 months, respectively.
These findings indicate that the PFS improvement was accompanied by a higher proportion of patients achieving a confirmed tumour response and a longer duration of response among responders.
However, overall survival (OS) data remained immature at the interim analysis. Although a favourable trend toward improved OS was reported with iza-bren, the available findings do not establish a definitive survival benefit. Further follow-up will be needed to determine whether the observed improvement in disease control translates into longer overall survival.
Safety Profile of Iza-Bren
The reported safety profile was described as manageable, with no new safety signals identified. Grade 3 or higher treatment-related adverse events were predominantly hematologic, and the announcement reported that 1.9% of patients receiving iza-bren discontinued treatment because of treatment-related adverse events.
Interstitial lung disease (ILD) was uncommon, with adjudicated cases reported in two patients (0.9%) receiving iza-bren. One case was Grade 1 and the other Grade 3.
These findings provide an initial overview of treatment tolerability. Nevertheless, the reported discontinuation rate and ILD incidence should not be interpreted in isolation from the full adverse-event profile, including the frequency and severity of hematologic toxicities.
About Izalontamab Brengitecan
Izalontamab brengitecan, also known as iza-bren or BL-B01D1, is an investigational bispecific ADC designed to target epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3).
Following target binding and internalization, the ADC delivers a topoisomerase I inhibitor (Topo1i) payload intended to induce cytotoxic stress and cancer cell death. Its dual-targeting design also inhibits EGFR and HER3 signaling pathways associated with tumour cell proliferation and survival.
Clinical development has evaluated iza-bren across several tumour types, including previously treated EGFR-mutated NSCLC, nasopharyngeal carcinoma, esophageal squamous cell carcinoma, triple-negative breast cancer and hormone receptor-positive/HER2-negative breast cancer.
The US Food and Drug Administration (FDA) has granted iza-bren Breakthrough Therapy Designation for previously treated advanced EGFR-mutated NSCLC. This designation supports expedited development and regulatory review but does not constitute marketing approval.
Clinical Interpretation
The PANKU-Lung01 findings provide evidence that iza-bren may offer improved disease control compared with platinum-based chemotherapy in patients with EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment. The improvement in PFS, together with higher response rates and longer response duration, supports further evaluation of this investigational ADC in this treatment setting.
The principal remaining uncertainty is whether the PFS benefit will translate into a meaningful overall survival advantage. The immature OS data and the need to assess the complete safety profile remain important considerations in interpreting the results. Further follow-up and regulatory assessment will help clarify the therapy’s potential clinical role.
References
Bristol Myers Squibb. Izalontamab Brengitecan (Iza-Bren) Doubles Median Progression-Free Survival in Patients with Previously Treated EGFR-Mutated Non-Small Cell Lung Cancer Compared to Chemotherapy in the Phase 3 PANKU-Lung01 Study. October 26, 2026
A Study Comparing BL-B01D1 With Platinum Based Chemotherapy in Patients with Locally Advanced or Metastatic Non-small Cell Lung Cancer (PANKU-Lung01), ClinicalTrials.gov ID NCT06382116
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.