Abstract LB366: Fianlimab + cemiplimab in patients (pts) with advanced (adv) melanoma (Mel): Subgroup analyses by blinded independent central review (BICR)
Authors: Meredith McKean, Amy M. Weise, Kyriakos P. Papadopoulos, John Crown, Sajeve S. Thomas, Janice Mehnert, John M. Kaczmar, Kevin B. Kim, Nehal J. Lakhani, Melinda L. Yushak, Jayakumar Mani, Fang Fang, Shuquan Chen, Jingxiao Chen, Laura Brennan, JuAn Wang, Israel Lowy, Mark Salvati, Matthew G. Fury, Karl D. Lewis, Omid Hamid
Journal: Cancer Research (2025)

Abstract Background: Treatment (Tx) with fianlimab (anti-LAG-3) + cemiplimab (anti-PD-1) resulted in a 57% ORR by BICR in pts with adv Mel, with an acceptable risk-benefit profile. Here, we present an efficacy analysis by BICR in subgroups of pts with adv Mel (neoadjuvant/adjuvant pretreated [NAP], elevated LDH, BRAF status, adrenal insufficiency [AI], and ctDNA status). Methods: Three independent expansion cohorts of pts who were anti-PD-(L)1 Tx-naïve for adv Mel (NCT03005782) received fianlimab 1600 mg + cemiplimab 350 mg IV every 3 weeks (wks) for ≤24 months (mos). Results: Overall, 98 pts were enrolled (median age: 68 years). At the data cutoff (Oct 31, 2023), median follow-up was 23 mos, and median Tx duration was 36 wks. 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 discontinuations (22%) were due to TEAEs. Overall BICR-assessed median PFS (mPFS), median OS (mOS), CR rate, and ORR were 24 mos (95% CI 12-NE), NR (95% CI 42-NE), 25%, and 57% (95% CI 47-67), respectively. Estimated survival probability was 83% at 12 mos and 71% at 24 mos. A total of 31% and 4% of pts completed 1 and 2 years of Tx, respectively. In NAP pts who had received anti-PD-(L)1 Tx (n=13), the mPFS, CR rate, and ORR were NR (95% CI 1-NE), 31%, and 46% (95% CI 19-75), respectively. There were no differences in mOS in NAP pts (NR [95% CI 26-NE]) versus NAP-naïve pts (NR [95% CI 31-NE]). In NAP and NAP-naïve pts, mPFS was NR (95% CI 3-NE) and 24 mos (95% CI 12-NE), respectively. In pts with LDH &amp;gt; ULN (n=31), the mPFS, mOS, CR rate, and ORR were 14 mos (95% CI 4-NE), 42 mos (95% CI 23-NE), 13%, and 55% (95% CI 36-73), respectively. In pts with BRAF mutation (n=48), the mPFS, mOS, CR rate, and ORR were NR (95% CI 39-69), NR (95% CI NE-NE), 31%, and 54% (95% CI 46-70), respectively. In pts with any-grade drug-related AI (n=12), the mPFS, mOS, CR rate, and ORR were NR (95% CI 8-NE), NR (95% CI 21-NE), 58%, and 92% (95% CI 62-100), respectively. The mPFS was NR in pts with PD-L1 expression &amp;lt;1% (95% CI 4-NE) and ≥1% (95% CI 24-NE), and in pts with LAG-3 expression &amp;lt;1% (95% CI 1-NE) and ≥1% (95% CI 19-NE). The mOS was NR in pts with PD-L1 expression &amp;lt;1% (95% CI 23-NE) and ≥1% (95% CI NE-NE), and in pts with LAG-3 expression &amp;lt;1% (95% CI 12-NE) and ≥1% (95% CI NE-NE). The ORR was 50% and 71% in pts with PD-L1 expression &amp;lt;1% and ≥1%, and 50% and 61% in pts with LAG-3 expression &amp;lt;1% and ≥1%, respectively. By Day 1 of Cycle 4, ctDNA was cleared in 15/31 pts. The mOS and mPFS for pts with uncleared ctDNA was 20.8 mos and 2.6 mos, respectively. The mOS and mPFS were NR in pts who were ctDNA-negative at Wk 9. Conclusions: With longer follow-up, fianlimab + cemiplimab continued to demonstrate high clinical activity and a generally acceptable safety profile in subgroups of pts with adv Mel. AI was reported in 12% of pts receiving the Tx; efficacy rates were higher in pts who experienced AI than in the overall study population. Citation Format: Meredith McKean, Amy M. Weise, Kyriakos P. Papadopoulos, John Crown, Sajeve S. Thomas, Janice Mehnert, John M. Kaczmar, Kevin B. Kim, Nehal J. Lakhani, Melinda L. Yushak, Jayakumar Mani, Fang Fang, Shuquan Chen, Jingxiao Chen, Laura Brennan, JuAn Wang, Israel Lowy, Mark Salvati, Matthew G. Fury, Karl D. Lewis, Omid Hamid. Fianlimab + cemiplimab in patients (pts) with advanced (adv) melanoma (Mel): Subgroup analyses by blinded independent central review (BICR) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB366.