Efficacy and Safety of Cosibelimab 800 Mg Every 2 Weeks for Locally Advanced Cutaneous Squamous Cell Carcinoma: Updated Follow-Up from a Pivotal Study.

9585 Background: Cosibelimab, a high-affinity programmed death ligand-1 (PD-L1)–blocking antibody, is approved by the US Food and Drug Administration (FDA) at a recommended dose of 1200 mg every 3 weeks (Q3W) for the treatment of adults with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC or mCSCC) who are not candidates for curative radiation or surgery. The CSCC expansion cohort of the pivotal open-label Phase 1 study (NCT03212404) evaluated cosibelimab 800 mg every 2 weeks (Q2W) in patients with laCSCC or mCSCC and 1200 mg Q3W in patients with mCSCC. Results through March 2023 demonstrated robust and sustained responses with cosibelimab 800 mg Q2W. The 800-mg Q2W and 1200-mg Q3W regimens are considered similar based on pharmacokinetic criteria outlined by the FDA for alternative PD-L1–blocking antibody dosing regimens. We present new follow-up data for the 800-mg Q2W laCSCC cohort. Methods: Eligible patients were ≥18 years old and had an Eastern Cooperative Oncology Group performance status of 0 or 1 and unresectable laCSCC not amenable to local therapy. Cosibelimab 800 mg was administered intravenously on Day 1 of each 14-day cycle until complete response, worsening disease progression, toxicity, or clinical deterioration. The primary endpoint was objective response rate (ORR; best overall response: complete or partial) by independent central review per RECIST V1.1; duration of response (DOR) was the key secondary endpoint. Follow-up data presented are from investigator assessment. Other secondary endpoints included safety. Results: By the January 31, 2025, data cutoff, 64 patients with laCSCC received ≥1 dose of cosibelimab 800 mg Q2W; their median (range) age was 77 (51–95) years, and 66% were male. Patients received a median of 29 (2–89) doses over a median duration of 60 (4–184) weeks. The ORR (95% confidence interval) was 50% (37%, 63%), including 17 complete and 15 partial responses; over a median follow-up duration of 31 (1–59) months the median DOR was not reached. Treatment-emergent adverse events (TEAEs) were reported in 61 (95%) patients and considered treatment-related in 50 (78%) patients; none were fatal. The most common AEs were anemia and diarrhea, recorded in 17 (27%) patients each. Grade ≥3 TEAEs were reported in 26 (41%) patients and considered treatment-related in 7 (11%). Hypertransaminasemia, in 2 (3%) patients, was the only serious treatment-related TEAE reported. Immune-related AEs (irAEs) were recorded in 22 (34%) patients; Grade ≥3 irAEs occurred in 1 (2%) patient and were dermatologic in nature (maculo-papular and pruritic rashes) and considered treatment-related. Conclusions: Responses to treatment with cosibelimab 800 mg Q2W remained robust and durable with stable ORR after continued follow-up in a larger cohort of patients with laCSCC, with no new safety signals identified. Clinical trial information: NCT03212404 .