Phase 1b trial of anti‐HER2 antibody inetetamab and pan‐HER inhibitor pyrotinib in HER2‐positive advanced lung cancer

Abstract There remains an unmet need for targeted therapies against advanced non‐small‐cell lung cancer (NSCLC) with HER2 mutations. To improve the antitumor activity of single anti‐HER2 agent, this prospective, single‐arm clinical trial (NCT05016544) examined the safety profile and efficacy of anti‐HER2 antibody inetetamab and pan‐HER TKI pyrotinib in HER2‐posivite advanced NSCLC patients. Enrolled patients received inetetamab every 3 weeks and pyrotinib once per day (pyrotinib, dose‐escalation part, 240 mg, 320 mg; dose‐expansion part, 320 mg). Primary endpoints were dose‐limiting toxicity (DLT) dosage and safety. Secondary endpoints included progression‐free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 48 patients were enrolled. During the dose‐escalation period, no DLT occurred. Diarrhea was the most commonly reported treatment‐related adverse event (TRAE). Grade 3 TRAEs occurred in seven patients. The median PFS (mPFS) was 5.5 months [95% confidence interval (CI): 4.4–8.6 months]. The confirmed ORR and DCR reached 25% (11/44) and 84.1% (37/44), respectively. Responses were shown in patients with distinct HER2 aberrations. In summary, inetetamab in combination with pyrotinib demonstrated acceptable safety and antitumor activity among patients with advanced HER2‐mutant NSCLC.