Work

A Randomized, Double-Blind, Phase 2 Study of Perioperative MK-4280A (Coformulation of Favezelimab and Pembrolizumab) vs Pembrolizumab in Patients With Resectable Cutaneous Squamous Cell Carcinoma

Year: 2024

Type: article

Abstract: Background: The immune checkpoint receptor lymphocyte-activation gene 3 (LAG3) is upregulated in many tumor types including cutaneous squamous cell carcinoma (cSCC) and frequently coexpressed with PD-L1. In the RELATIVITY-047 study, relatlimab (anti‒LAG3 antibody) + nivolumab (anti‒PD-1 antibody) prolonged PFS vs nivolumab in unresectable advanced melanoma; a phase 2 study additionally showed high pathological complete response (pCR) rate in resectable disease. Studies have also demonstrated antitumor activity and manageable safety with favezelimab (anti–LAG3 antibody) + pembrolizumab (anti‒PD-1 antibody). Cohort A of the basket study MK-4280A-010 (NCT06036836) is evaluating MK-4280A (fixed-dose coformulation of favezelimab + pembrolizumab) vs pembrolizumab for resectable cSCC. Methods: Cohort A of this randomized, double-blind, phase 2 study will enroll patients aged ≥18 yrs with histologically confirmed stage II–IV resectable cSCC as the primary malignancy (without M1; staging per AJCC 8th ed. for head/neck tumors or UICC 8th ed. for other tumor sites) and no prior systemic therapy or radiotherapy to the index lesion. Patients must have ECOG PS 0/1 and a tumor sample for biomarker analysis. Approximately 40 patients per arm will be randomized 1:1 (stratified by non-nodal vs nodal disease and head/neck vs other tumor site) to MK-4280A (favezelimab 800 mg + pembrolizumab 200 mg) or pembrolizumab 200 mg IV Q3W for ≤3 cycles in the neoadjuvant period, followed by surgical resection; then MK-4280A or pembrolizumab, as allocated, Q3W for ≤14 cycles in the adjuvant period (adjuvant radiotherapy per investigator discretion is permitted if no pCR by local assessment). Total treatment duration will be approximately ≤1 yr or until PD/recurrence or intolerable AEs. Imaging occurs after the last neoadjuvant cycle before surgery, then Q12W during the adjuvant period through ≤1 yr. AEs are assessed throughout the study and graded per NCI CTCAE v5.0. Primary endpoint is pCR (no viable tumor in resected sample) by blinded central pathology review (BCPR). Secondary endpoints are pCR or clinical CR (no residual tumor per clinical exam/imaging) with negative biopsy, EFS and ORR (before surgery) per RECIST v1.1 by investigator review, major pathological response (≤10% viable tumor in resected sample) by BCPR, OS, and safety. Enrollment began in Sep 2023. Results: Pending Conclusions: Pending

Source: EJC Skin Cancer

DOI: 10.1016/j.ejcskn.2024.100214