Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Non–Small Cell Lung Cancer: AMBER Part 2B

Abstract Purpose: Treatment options for patients with non–small cell lung cancer (NSCLC) who have progressed on anti–PD-(L)1 treatment are lacking. In preclinical models, blockade of the inhibitory immune receptor T-cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) is associated with an antitumor response. AMBER (NCT02817633) part 2B assessed the safety and efficacy of cobolimab, an anti–TIM-3 humanized monoclonal antibody, plus PD-1 inhibitor dostarlimab in patients with locally advanced or metastatic NSCLC who had progressed on anti–PD-(L)1 treatment. Patients and Methods: Adult patients with anti–PD-(L)-1 treated locally advanced or metastatic NSCLC were included. Patients received cobolimab 100, 300, or 900 mg and dostarlimab 500 mg every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, patient withdrawal, investigator’s decision, or death. Endpoints included overall response rate, disease control rate, and safety. Post hoc biomarker assessments of pretreatment tumor biopsies were also assessed. Results: In total, 85 patients were enrolled and 84 received treatment. Treatment-emergent and treatment-related adverse events occurred in 98.8% and 52.4% of patients, respectively; no treatment-related deaths occurred. Across all three cobolimab doses, overall response rate was 8.3% (95% confidence interval, 3.4–16.4) and disease control rate was 21.4% (95% confidence interval, 13.2–31.7); both were highest in the 300 mg cohort (n = 41; 9.8% and 22.0%). Pretreatment TIM-3 expression was significantly greater in patients with partial or stable responses versus progressive disease. Conclusions: Cobolimab plus dostarlimab showed preliminary efficacy and tolerability in a subset of patients with locally advanced/metastatic NSCLC. See related article by Davar et al., p. 3433