Phase 1 study of fianlimab (anti-LAG- 3) plus cemiplimab (anti-PD- 1) in advanced melanoma: Post-adjuvant PD-1 and poor prognosis subgroup analyses
Recommended Citation
Hamid O, Weise A, McKean M, Papadopoulos KP, Crown J, Thomas S, Kaczmar J, Kim KB, Lakhani NJ, Yushak M, Kim TM, Rabinowits G, Spira A, Mehmi I, Fang F, Mani J, Brennan L, Jankovic V, Paccaly A, Masinde S, Lewis KD, Salvati M, Fury MG, Lowy I, Gullo G. Phase 1 study of fianlimab (anti-LAG- 3) plus cemiplimab (anti-PD- 1) in advanced melanoma: Post-adjuvant PD-1 and poor prognosis subgroup analyses. Pigment Cell and Melanoma Research 2024; 37(1):217-218.
Document Type
Conference Proceeding
Publication Date
1-11-2024
Publication Title
Pigment Cell and Melanoma Research
Keywords
cemiplimab, fianlimab, lactate dehydrogenase, lymphocyte activation gene 3 protein, adult, aged, cohort analysis, conference abstract, drug combination, drug therapy, drug toxicity, female, follow up, human, liver metastasis, major clinical study, male, melanoma, middle aged, monotherapy, phase 1 clinical trial, phase 3 clinical trial, prognosis, response evaluation criteria in solid tumors, systemic therapy
Abstract
Previously, we reported an ORR of 63.8% in patients (pts) with anti-PD- ( L)1-naïve advanced melanoma (Mel) treated with anti-LAG- 3 (fianlimab) + anti-PD- 1 (cemiplimab) antibodies (NCT03005782). Here, we report updated safety and efficacy data from three expansion cohorts: anti-PD- ( L)1-naïve pts (MM1); systemic treatment (Tx)-naïve pts (MM2); pts with prior (neo)adjuvant (adj) systemic Tx, including anti-PD- 1, who had a disease-and treatment-free interval >6 months (mos; MM3). We also report ad hoc subgroup analyses by presence of poor prognosis factors at baseline. Pts with advanced non-uveal Mel were treated with fianlimab 1600 mg + cemiplimab 350 mg IV every 3 weeks (wks) for 12 mos (+ optional 12 mos further if clinically indicated). Tumors were assessed per RECIST 1.1 every 6 wks for 24 wks, then every 9 wks. As of Nov 1, 2022 data cutoff, 40 pts each in cohorts MM1 and MM2, and 18 pts in cohort MM3 were treated with fianlimab + cemiplimab. Prior systemic (neo)adj Tx for Mel was received by 23.5% of pts. Median (IQR) follow-up and Tx durations were 12.6 mos (8.6-19) and 32.9 wks (15-54), respectively. In a combined ad hoc analysis of 98 pts, RECIST 1.1-based ORR was 61.2%, with median DOR (mDOR) not reached (NR) (95% CI 22.6-not estimated [NE]) and median PFS (mPFS; Kaplan-Meier estimate) 15.3 (95% CI 9.4-NE) mos. In pts with prior anti-PD- 1 adj Tx (n = 13), ORR, mDOR and mPFS were 61.5%, NR and 11.8 mos, respectively. In the subgroup of pts with LDH > ULN (n = 32), ORR, DCR and mPFS were 53.1%, 71.9% and 11.8 mos (95% CI 3.7-NE), respectively. In pts with liver metastases (n = 21), ORR, DCR and mPFS were 42.9%, 57.1% and 4.2 mos, respectively. In pts with visceral organ metastases and LDH > ULN (n = 17), ORR, DCR and mPFS were 35.3%, 58.8% and 7.1 mos, respectively. Overall, 43.9%, 32.7% and 65.3% of pts experienced Grade ≥3 TEAEs, serious TEAEs and immune-related AEs, respectively. High clinical activity of fianlimab + cemiplimab was shown in pts with advanced Mel post-adj anti-PD- 1 Tx and in pts with poor prognosis features. Our results demonstrate encouraging clinical activity relative to other immune checkpoint monotherapies or combinations used in this clinical setting. Phase 3 trials of fianlimab + cemiplimab in Tx-naïve advanced Mel (NCT05352672) and in the high-risk adjuvant setting (NCT05608291) are ongoing .
Volume
37
Issue
1
First Page
217
Last Page
218
