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Updated: Sep 18, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer:
Diwakar Davar1, Zeynep Eroglu2, Mohammed Milhem3
1Department of Medicine - Hematology/Oncology, Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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.
Insights
Cobolimab combined with dostarlimab demonstrated preliminary efficacy and tolerability in patients with advanced non-small cell lung cancer (NSCLC) who progressed on anti-PD-(L)1 therapy. Higher TIM-3 expression correlated with better response to this novel treatment strategy.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Limited treatment options exist for non-small cell lung cancer (NSCLC) patients after anti-PD-(L)1 therapy failure.
- Preclinical studies suggest blocking T-cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) can elicit an antitumor response.
Purpose of the Study:
- To assess the safety and efficacy of cobolimab (anti-TIM-3 antibody) plus dostarlimab (PD-1 inhibitor) in patients with advanced NSCLC.
- To evaluate cobolimab's efficacy in combination with a PD-1 inhibitor in a heavily pretreated NSCLC population.
Main Methods:
- The AMBER trial (Part 2B) enrolled adult patients with locally advanced or metastatic NSCLC previously treated with anti-PD-(L)1 therapy.
- Patients received cobolimab at varying doses (100, 300, 900 mg) plus dostarlimab (500 mg) every 3 weeks until disease progression or unacceptable toxicity.
- Primary endpoints included overall response rate (ORR) and disease control rate (DCR), with post hoc biomarker analysis of TIM-3 expression.
Main Results:
- Eighty-four patients received treatment; 98.8% experienced treatment-emergent adverse events, with no treatment-related deaths.
- The overall response rate was 8.3% and the disease control rate was 21.4% across all cobolimab doses.
- The 300 mg cobolimab cohort showed the highest ORR (9.8%) and DCR (22.0%).
- Higher pretreatment TIM-3 expression was associated with partial or stable responses compared to progressive disease.
Conclusions:
- Cobolimab plus dostarlimab demonstrated preliminary efficacy and tolerability in a subset of patients with advanced NSCLC.
- The combination therapy warrants further investigation, particularly in patients with higher TIM-3 expression.
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