Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

Abstract

BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches

“…The approved fixed dose regimen is 350 mg intravenously every three weeks. Durable responses and similar safety profile have been observed in both weight-based and fixed-dosing groups [ 161 ].…”

Comprehensive Mutational and Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell Carcinoma Cell Lines Reveal Novel Drug Susceptibilities

“…Primary cSCC is typically treatable, although in 2–5% of cases metastatic spread occurs [ 3 , 4 , 5 , 6 , 7 , 8 ], resulting in the majority of disease-specific deaths. Other than surgery and radiotherapy, the only systemic therapy approved for locally advanced and metastatic cSCC is Cemiplimab immunotherapy, which resulted in a 50% response rate and was associated with adverse events [ 9 , 10 ].…”

Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

“…This cancer type was studied due to known high mutational burden. A response was seen in half of the patients in the pivotal phase II study with an acceptable safety profile (70,71).…”