KEY TAKEAWAYS
- AMBER Phase 1 and COSTAR Phase 2/3 evaluated cobolimab plus dostarlimab safety and efficacy in advanced/metastatic NSCLC patients.
- Primary endpoint: RECIST v1.1 ORR. Secondary: DCR, ir-ORR, irDCR, OS, safety. Exploratory: Post hoc biomarker assessments.
- Preliminary efficacy and safety seen with cobolimab plus dostarlimab in advanced NSCLC. The ongoing COSTAR study is assessing treatment versus standard care.
Researchers aimed to evaluate the safety and efficacy of cobolimab in combination with dostarlimab for patients with advanced/metastatic NSCLC under the AMBER trial (NCT02817633), a Phase 1 study involving dose escalation and expansion. They assessed cobolimab monotherapy and combinations in patients with advanced solid tumors.
In AMBER part 2B, the combination of cobolimab and dostarlimab was tested in patients with advanced/metastatic NSCLC who had previously undergone anti-PD(L)-1 therapy. Eligible patients received cobolimab (100, 300, or 900 mg IV) along with dostarlimab (500 mg IV) every three weeks (Q3W).
Primary endpoints were the objective response rate (ORR) per RECIST v1.1, while secondary endpoints included disease control rate (DCR), immune-related (ir)-ORR, and irDCR per irRECIST, overall survival (OS), and safety. Exploratory endpoints comprised post hoc biomarker assessments.
Eighty-four patients, with a mean age of 65.9 years (range: 35–86), received treatment. Predominant histologies included adenocarcinoma (69.0%) and squamous cell carcinoma (26.2%), with 58.3% having undergone ≥3 prior treatment lines. As of the data cut-off in February 2023, the overall response rate (ORR) was 8.3%, immune-related ORR (irORR) was 9.5%, disease control rate (DCR) was 21.4%, and immune-related DCR (irDCR) was 25.0%. The highest ORR (9.8%) occurred in the cobolimab 300 mg cohort, subsequently chosen as the recommended Phase 2 dose.
Patients displaying partial response or stable disease based on irRECIST (n=12) had elevated baseline TIM-3 immunohistochemistry levels compared to those with progressive disease (n=22; p=0.013); a similar trend was noted for ORR. Additionally, patients with baseline systemic interleukin (IL)-6 and IL-8 levels below the median exhibited a higher overall survival compared to those with levels above the median.
Treatment-emergent adverse events (TEAEs) of grade ≥1 manifested in 98.8% of patients, with the most prevalent being fatigue (42.9%), dyspnea (31.0%), and decreased appetite (27.4%). Notably, 54.8% of patients experienced Grade ≥3 TEAEs. Specifically related to treatment, 52.4%, 13.1%, and 7.1% of patients encountered treatment-related adverse events (TRAEs), Grade ≥3 TRAEs, and serious TRAEs, respectively, with no observed TRAE-related deaths.
Early evidence of efficacy and acceptable safety was observed in patients with advanced/metastatic NSCLC treated with cobolimab plus dostarlimab. The ongoing Phase 2/3 study, COSTAR (NCT04655976), is currently evaluating cobolimab plus dostarlimab and docetaxel versus the standard of care for patients with advanced NSCLC.
Source: https://jitc.bmj.com/content/11/Suppl_1/A678
Clinical Trial: https://clinicaltrials.gov/study/NCT02817633
https://clinicaltrials.gov/study/NCT04655976
Davar D, Eroglu Z, Milhem M, et al596 AMBER, Part 2B: a phase 1 study of cobolimab plus dostarlimab in patients with advanced/metastatic non-small cell lung cancer (NSCLC) previously treated with anti-PD(L)-1 therapyJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0596.
