KEY TAKEAWAYS
- The phase 3 study will evaluate the use of fianlimab and cemiplimab combination in high-risk, resected Mel.
- The primary endpoint is investigator-assessed RFS, and the secondary endpoints are efficacy safety, pharmacokinetic, immunogenicity, and patient reported outcomes.
- The first analysis will be conducted after observing 242 RFS events.
Surgery is often the first line of defense for patients with newly diagnosed melanoma. However, there is a risk of relapse even after curative surgery. To combat this, postoperative adjuvant therapy with immune checkpoint inhibitors has been shown to improve relapse-free and distant metastasis-free survival for high-risk patients. Two high-affinity, fully human, IgG4 monoclonal antibodies, fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1), have shown promising results in a phase 1 study for advanced Mel. Furthermore, the combination of anti-LAG-3 and anti-PD-1 therapy has shown superiority over anti-PD-1 therapy alone for progression-free survival in advanced Mel. Based on these findings, a combination of fianlimab and cemiplimab may be a promising approach for high-risk adjuvant Mel.
This phase 3 double-blind trial will compare fianlimab + cemiplimab with pembrolizumab for adjuvant therapy in high-risk resected Mel, spanning 200 sites.
The eligibility criteria for this study require patients (pts) to meet specific criteria in order to participate. These criteria include being at least 12 years of age, having stage IIc, III, or IV melanoma that has been completely resected within the last 12 weeks, and not having received any prior systemic anti-cancer or radiation therapy for melanoma in the previous 5 years. Additionally, patients must not have evidence of metastatic disease on staging investigations and must have an Eastern Cooperative Oncology Group performance status (PS) of 0 or 1 (for adult patients), Karnofsky PS >70 (patients over 16 years of age) or Lansky PS >70 (patients under 16 years of age).
The placebo controlled trial will enrol about 1530 pts, randomized 1:1:1 to study arms (all Rx Q3W IV): A. fianlimab (dose 1) + cemiplimab (350 mg); B. fianlimab (dose 2) + cemiplimab (350 mg); C. pembrolizumab (200 mg) + saline/dextrose placebo. The trial will last for up to one year and will stratify patients based on disease stage (IIIA vs IIC-IIIB-IIIC vs IIID-IV [M1a/b] vs IV [M1c/d]) and geography (North America vs Europe vs Rest of World).
The study’s primary endpoint is investigator-assessed RFS. The secondary endpoints are efficacy (overall survival, DMFS, melanoma-specific survival), safety, pharmacokinetic, immunogenicity, and patient reported outcomes. The first analysis will be conducted when 242 RFS events have been observed.
Source: https://eado2023.com/wp-content/uploads/2023/04/Abstract-Band_EADO2023_Stand-21-04-2023-kl.pdf
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05608291
MD Timothy Panella1, Dr Sajeve S Thomas2, Dr Meredith McKean3, Kim Margolin4, Ryan Weight5, Jayakumar Mani6, Shraddha Patel6, Priya Desai6, Mark Salvati6, Israel Lowy6, Matthew Fury6, Giuseppe Gullo6 1 University Of Tennessee Medical Center, Knoxville, United States / 2 Orlando Health Cancer Institute, Lake Mary, United States / 3 Sarah Cannon Research Institute/Tennessee Oncology PLLC, Nashville, United States / 4 Saint John’s Cancer Institute, Santa Monica, United States / 5 The Melanoma and Skin Cancer Institute, Denver, United States / 6 Regeneron Pharmaceuticals, Inc., Tarrytown, United States.
