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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Izalontamab Brengitecan in Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Actionable Genomic
Huaqiang Zhou1, Hongyun Zhao2, Xue Hou1
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Purpose:
To evaluate the safety and efficacy of izalontamab brengitecan (iza-bren) in patients with non-small cell lung cancer (NSCLC) harboring actionable genomic alterations (GAs) outside of classical epidermal growth factor receptor (EGFR) mutations.
Methods:
Eligible patients had locally advanced or metastatic NSCLC with prespecific actionable GAs, had progressed after standard treatment and received no more than one previous line of chemotherapy. iza-bren was administered at the dose of 2.5 mg/kg once per day on days 1 and 8 of each 3-week cycle. The primary end point was safety. The secondary end points included objective response rate (ORR), disease control rate (DCR), and duration of response. The exploratory end points included progression-free survival (PFS) and overall survival (OS).
Results:
A total of 83 patients with NSCLC were enrolled in four cohorts: EGFR exon20ins/nonclassical mutations (n = 14), human epidermal growth factor receptor 2 (HER2) mutation (n = 19), KRAS/BRAF/MET mutation (n = 26), and ALK/ROS1/RET/NTRK fusion (n = 24). The most common grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (51.8%), anemia (44.6%), and neutropenia (43.4%). The most frequent nonhematologic TRAEs of all grades were nausea (49.4%), asthenia (45.8%), stomatitis (44.6%), and diarrhea (38.6%). One case of grade 2 interstitial lung disease was observed. The confirmed ORR was 39.7%, and the DCR was 85.9%. The median PFS was 7.0 months (95% CIs, 5.4 to 10.5), while OS data were immature. Patients with EGFR exon20ins or other nonclassical mutations achieved an ORR of 69.2% with a median PFS of 10.5 months (95% CI, 6.9 to not reached); the HER2-mutant cohort had an ORR of 52.9% and a median PFS of 7.5 months (95% CI, 5.4 to not reached).
Conclusion:
iza-bren demonstrated encouraging antitumor activity and a manageable safety profile in pretreated NSCLC patients with diverse GAs outside of classical EGFR mutations, especially in EGFR exon20ins/nonclassical and HER2 mutations.
Insights
Izalontamab brengitecan shows promising results in non-small cell lung cancer (NSCLC) patients with specific genetic mutations. This treatment offers a manageable safety profile and encouraging antitumor activity for patients with diverse genomic alterations.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide.
- Targeted therapies have revolutionized NSCLC treatment, but resistance and diverse genomic alterations present ongoing challenges.
- Identifying effective treatments for NSCLC patients with actionable genomic alterations beyond classical EGFR mutations is crucial.
Purpose of the Study:
- To assess the safety and efficacy of izalontamab brengitecan (iza-bren) in pretreated NSCLC patients.
- To evaluate iza-bren in patients with actionable genomic alterations (GAs) outside of common EGFR mutations.
- To determine the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of iza-bren.
Main Methods:
- A phase II clinical trial enrolled 83 NSCLC patients with locally advanced or metastatic disease and specific actionable GAs.
- Patients had progressed on standard therapy and received limited prior chemotherapy.
- Izalontamab brengitecan was administered at 2.5 mg/kg on days 1 and 8 of 3-week cycles, with safety and efficacy endpoints evaluated.
Main Results:
- The study included cohorts with EGFR exon20ins/nonclassical mutations, HER2 mutations, KRAS/BRAF/MET mutations, and ALK/ROS1/RET/NTRK fusions.
- The most frequent grade ≥3 treatment-related adverse events (TRAEs) were thrombocytopenia (51.8%), anemia (44.6%), and neutropenia (43.4%).
- The overall confirmed ORR was 39.7% and DCR was 85.9%, with a median PFS of 7.0 months. Notably, EGFR exon20ins/nonclassical and HER2-mutant cohorts showed higher ORRs (69.2% and 52.9%, respectively).
Conclusions:
- Izalontamab brengitecan demonstrates encouraging antitumor activity in pretreated NSCLC patients with various GAs outside of classical EGFR mutations.
- The drug exhibits a manageable safety profile, with key toxicities including hematologic events and gastrointestinal issues.
- Particular efficacy was observed in patients with EGFR exon20ins/nonclassical and HER2 mutations, suggesting potential for these subgroups.
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