Journal article
Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer: AMBER Part 2B
Clinical cancer research, Vol.31(16), pp.3443-3451
08/15/2025
DOI: 10.1158/1078-0432.CCR-25-0806
PMCID: PMC12351275
PMID: 40552922
Abstract
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.
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.
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.
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. XX.
Details
- Title: Subtitle
- Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer: AMBER Part 2B
- Creators
- Diwakar Davar - University of Pittsburgh Medical CenterZeynep Eroglu - Moffitt Cancer CenterMohammed Milhem - University of IowaCarlos Becerra - The US Oncology NetworkMartin Gutierrez - Hackensack Meridian HealthAntoni Ribas - University of California, Los AngelesBrian Di Pace - GlaxoSmithKline (United States)Tianli Wang - GSK, Waltham, MassachusettsHailei Zhang - GSK, Waltham, MassachusettsSrimoyee Ghosh - GSK, Waltham, MassachusettsNiranjan Yanamandra - GlaxoSmithKline (United States)Theo Borgovan - GSK, Waltham, MassachusettsShyam Srivats - GlaxoSmithKline (United States)Angela Waszak - GSK, Waltham, MassachusettsArindam Dhar - GlaxoSmithKline (United States)Patricia LoRusso - University of New Haven
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.31(16), pp.3443-3451
- DOI
- 10.1158/1078-0432.CCR-25-0806
- PMID
- 40552922
- PMCID
- PMC12351275
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- GSK - GSK
The authors would like to thank the patients and their families for consenting to the study and analysis, study coordinators, and the operations team in facilitating the study. The authors would like to acknowledge Lillian Cho, PharmD, and Alex Gyurdieva, MSc, at GSK for their review of the manuscript and Hasan H. Jamal, MSc, at GSK for coordination and review of the manuscript. Medical writing support was provided by Nakeirah Christie, PhD; Taylor Barrett, PhD; and Nicholas Thomas, PhD, of Fishawack Indicia Ltd., UK, part of Avalere Health, and was funded by GSK. This study (AMBER; GSK Study 213,348; NCT002817633) was funded by GSK.
- Language
- English
- Electronic publication date
- 06/24/2025
- Date published
- 08/15/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984833483902771
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