Fianlimab plus cemiplimab in patients with advanced melanoma: Subgroup analyses by blinded independent central review
Recommended Citation
McKean M, Weise A, Papadopoulos KP, Crown J, Thomas SS, Mehnert J, Kaczmar J, Kim KB, Lakhani NJ, Yushak M, Mani J, Fang F, Chen S, Chen J, Brennan L, Wang J, Lowy I, Salvati M, Fury MG, Lewis K, Hamid O. Fianlimab plus cemiplimab in patients with advanced melanoma: Subgroup analyses by blinded independent central review. J Dtsch Dermatol Ges 2025; 23(S6):130.
Document Type
Conference Proceeding
Publication Date
1-1-2025
Publication Title
J Dtsch Dermatol Ges
Abstract
Background: Treatment (Tx) with fianlimab (anti–LAG-3) + cemiplimab (anti–PD-1) exhibited durable 57% ORR in patients (pts) with advanced melanoma (adMEL) by BICR, with an acceptable risk–benefit profile. Here, we present an efficacy analysis by BICR in subgroups (neoadjuvant/adjuvant pretreated [NAP], elevated LDH, BRAF status, adrenal insufficiency [AI] and ctDNA status) of pts with adMel. Methods: Three independent expansion cohorts of adMEL anti–PD-(L)1 naïve pts (NCT03005782) received fianlimab 1600 mg + cemiplimab 350 mg IV every 3 weeks (wks) up to 24 months (mos). Results: Overall, 98 pts were enrolled. At data cutoff (Oct 31, 2023), median follow-up was 23 mos and median Tx duration was 36 wks. 31% and 4% of pts completed 1 and 2 years of Tx, respectively. Grade ≥ 3 TEAEs occurred in 47% of pts, serious TEAEs in 39%, and immune-mediated AEs in 39%. Of the 76 pts (78%) who discontinued Tx, 17 (22%) were due to TEAEs. BICR-assessed efficacy data for cohorts MM1, MM2 and MM3 are shown in Table 1 . Overall (n=98) median PFS (mPFS), CR rate, median OS (mOS), and ORR were 24 mos (95% CI 12–NE), 25%, NR (95% CI 42–NE) and 57% (95% CI 47–67), respectively. Estimated survival probability was 83% at 12 mos and 71% at 24 mos. Overall, 12 pts (12%) experiencing AI achieved an ORR of 92% (95% CI 62–100) and CR of 58%, with mPFS (95% CI 8–NE) and mOS (95% CI 21–NE) of NR. PFS and OS analysis per response by BICR is shown in Table 2. ORR was 50% and 71% in pts with PD-L1 expression <1% and ≥ 1%, and 50% and 61% in pts with LAG-3 expression <1% and ≥ 1%, respectively. mPFS was NR in pts with PD-L1 expression <1% (95% CI 4–NE) and ≥1% (95% CI 24–NE); and in pts with LAG-3 expression <1% (95% CI 1–NE) and ≥1% (95% CI 19–NE). mOS was NR in pts with PD-L1 expression <1% (95% CI 23–NE) and ≥1% (95% CI NE–NE); and in pts with LAG-3 expression <1% (95% CI 12–NE) and ≥ 1% (95% CI NE–NE). ctDNA was cleared by Cycle 4 Day 1 in 15/31 pts. mOS and mPFS for pts with uncleared ctDNA was 20.8 mos and 2.56 mos, respectively. mOS and mPFS were NR in pts who were ctDNA negative at Wk 9. Conclusions: With longer follow-up, fianlimab + cemiplimab continues to demonstrate high clinical activity in subgroups of pts with adMEL with a generally acceptable safety profile. While the AE of AI is reported in 12% of pts treated with the combination, we report higher efficacy rates in pts who experienced AI than the overall study population.
Volume
23
Issue
S6
First Page
130
