KEY TAKEAWAYS
- anti–LAG-3 + anti–PD is a phase III trial that evaluated the combination of anti-LAG-3 and anti-PD-1 as adjuvant therapy in high-risk Mel patients to improve relapse-free survival and distant metastasis-free survival considering overall survival, safety, pharmacology, and immunogenicity.
- This international trial at 200 sites will enroll eligible patients ≥12 years with completely resected high-risk Mel with three arms: fianlimab + cemiplimab, fianlimab + cemiplimab (different dose), and pembrolizumab + placebo.
- The primary endpoint is investigator-assessed RFS. Secondary endpoints include efficacy, safety, pharmacokinetics, immunogenicity, and patient-reported outcomes. First analysis at 242 RFS events.
Melanoma (Mel) is a deadly skin cancer that can recur after surgery. Immune checkpoint inhibitors may improve survival after surgery for high-risk melanoma.
This study aims to evaluate the combination of anti-LAG-3 and anti-PD-1 as adjuvant therapy in high-risk Mel patients to improve relapse-free survival and distant metastasis-free survival considering overall survival, safety, pharmacology, and immunogenicity.
This study (200 sites) will enroll eligible patients ≥12 years with completely resected high-risk melanoma (Stage IIc, III, or IV, all M-stages) and an ECOG performance status of 0 or 1 (for adult pts), Karnofsky PS >70 (pts >16 years) or Lansky PS >70 (pts <16 years). Patients must not have received prior systemic anti-cancer or radiation therapy for Mel in the last 5 years and should show no evidence of metastatic disease on staging investigations.
The trial will have three arms: fianlimab (1,600 mg) + cemiplimab (350 mg), fianlimab (400 mg) + cemiplimab (350 mg), and pembrolizumab (200 mg) + saline/dextrose placebo. Approximately 1,530 patients will be randomized 1:1:1 to Arms A:B:C and treated for up to 1 year. They will be stratified by disease stage (stage IIIA vs. IIC-IIIB-IIIC vs. IIID-IV [M1a/b] vs. IV [M1c/d]) and geography (North America vs. Europe vs. Rest of the World).
The study’s main focus is investigator-assessed recurrence-free survival (RFS) as the primary endpoint. Secondary endpoints encompass efficacy (overall survival, distant metastasis-free survival, melanoma-specific survival), safety (treatment-emergent adverse events, interruption/discontinuation of drugs due to TEAEs), pharmacokinetic data (concentrations of fianlimab and cemiplimab in serum over time), immunogenicity (anti-drug Abs and neutralizing Abs in serum against fianlimab or cemiplimab), and patient-reported outcomes. The first analysis will occur after observing 242 RFS events. These findings supported the use of fianlimab and cemiplimab combination in high-risk adjuvant Mel.
Source: https://meetings.asco.org/abstracts-presentations/226072
Clinical Trial: https://clinicaltrials.gov/study/NCT05608291
Timothy J. Panella, Sajeve Samuel Thomas, Meredith McKean, Kim Allyson Margolin, Ryan Michael Weight, Jayakumar Mani, Shraddha Patel, Priya Desai, Mark Salvati, Israel Lowy, Matthew G. Fury, and Giuseppe Gullo
Journal of Clinical Oncology 2023 41:16_suppl, TPS9598-TPS9598
