In a phase I trial reported in the Journal of Clinical Oncology, Omid Hamid, MD, and colleagues found that the combination of the human lymphocyte activation gene-3 (LAG-3)-targeting monoclonal antibody fianlimab plus the PD-1–targeting monoclonal antibody cemiplimab-rwlc was active in patients with advanced melanoma.
Omid Hamid, MD
Study Details
In the study, 113 patients from sites in the United States, United Kingdom, Ireland, South Korea, and Australia were allocated to four expansion cohorts between October 2018 and April 2022. The four cohorts consisted of an anti–PD-1–naive cohort (n =40), a systemic treatment–naive cohort (n = 40), a previous neoadjuvant/adjuvant treatment cohort (n = 18), and a previous anti–PD-1 therapy for advanced disease cohort (n = 15). Patients received fianlimab at 1,600 mg and cemiplimab at 350 mg once every 3 weeks for up to 51 weeks, with an optional additional 51 weeks if clinically indicated. The primary outcome measure of the study was objective response.
Key Findings
Objective response rates were 63% in the anti–PD-1-naive cohort (median follow-up = 20.8 months); 63% in the systemic treatment–naive cohort (median follow-up = 11.5 months); 56% in the previous neoadjuvant/adjuvant treatment cohort (median follow-up = 11.5 months); and 13% in the previous anti–PD-1 therapy for advanced disease cohort (median follow-up = 8 months). At a median follow-up of 12.6 months for the combined three cohorts who had not received previous anti–PD-1 therapy for advanced disease, the objective response rate was 61.2% and median progression-free survival was 13.3 months (95% confidence interval [CI] = 7.5 months to not evaluable).
Among 13 patients who had received previous anti–PD-1 adjuvant therapy, the objective response rate was 62% and median progression-free survival was 12 months (95% CI = 1.4 months to not evaluable). In contrast, in the cohort of patients who had received previous anti–PD-1 therapy for advanced disease, the objective response rate (as noted) was 13% and median progression-free survival was 1.5 months (95% CI = 1.3–7.7 months).
Among the three cohorts without patients who had received previous anti–PD-1 therapy for advanced disease, treatment-related grade ≥ 3 adverse events occurred in 22% of patients. Treatment discontinuation due to treatment-related adverse events occurred in 13%. Overall, apart from an increased incidence of adrenal insufficiency (12% grade 1 to 4, 4% grade 3 to 4), no new safety signals were observed.
The investigators concluded, “The current results show a promising benefit-risk profile of fianlimab/cemiplimab combination for patients with advanced melanoma, including those with previous anti–PD-1 therapy in the adjuvant, but not advanced, setting.”
Dr. Hamid, of The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Regeneron Pharmaceuticals Inc. For full disclosures of the study authors, visit ascopubs.org.
