Abstract LB-138: Adjuvant pembrolizumab or placebo in patients with high-risk, locally advanced cutaneous squamous cell carcinoma: Phase 3 KEYNOTE-630
Authors: Chang Anne Lynne S. , Daniels Gregory A. , Cohen Ezra E. , Ge Joy Yang , Gumuscu Burak , Swaby Ramona F. , Geiger Jessica L. 
Published: September 2020

Background: Local recurrence occurs within 5 years in ~20% of patients with high-risk locally advanced cutaneous squamous cell carcinoma treated with current standard-of-care surgical resection and adjuvant radiotherapy. Recent data with programmed death 1 inhibitors have demonstrated antitumor activity and an acceptable safety profile in patients with locally advanced or metastatic disease. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-630 trial (NCT03833167) will evaluate the efficacy and safety of adjuvant pembrolizumab monotherapy in patients with high-risk locally advanced cutaneous squamous cell carcinoma. Trial design: Patients with resectable high-risk locally advanced cutaneous squamous cell carcinoma who have undergone surgical resection and radiotherapy will be randomly assigned 1:1 to intravenous pembrolizumab (400 mg every 6 weeks) or placebo for up to 9 cycles (~1 year) or until disease recurrence, unacceptable toxicity, or withdrawal by the investigator or the patient. Randomization will be stratified by extracapsular extension (yes vs no), cortical bone invasion (yes vs no), and prior systemic therapy (yes vs no). Key eligibility criteria include histologically confirmed locally advanced cutaneous squamous cell carcinoma with ≥1 high-risk feature as the primary site of malignancy and complete macroscopic resection of all known cutaneous squamous cell carcinoma disease, with or without microscopic positive margins, who completed ≥45 Gy adjuvant radiotherapy, were disease free ≤28 days from randomization, and have Eastern Cooperative Oncology Group performance status 0 or 1. The primary end point is recurrence-free survival based on investigator assessment with biopsy confirmation. Secondary end points are overall survival, health-related quality of life, and safety. Radiographic imaging will be performed at least every 12 weeks in years 1 and 2, then every 6 months until the end of year 5 to assess treatment response. Patients who are ineligible for surgical resection following documented disease recurrence may cross over to receive re-treatment with open-label intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles (~2 years). Adverse events will be recorded until 30 days (90 days for serious adverse events) after study end and will be graded per NCI CTCAE v4.0. Enrollment of ~570 patients is planned, and recruitment is ongoing in 20 countries.

Citation Format: Anne Lynne S. Chang, Gregory A. Daniels, Ezra E. Cohen, Joy Yang Ge, Burak Gumuscu, Ramona F. Swaby, Jessica L. Geiger. Adjuvant pembrolizumab or placebo in patients with high-risk, locally advanced cutaneous squamous cell carcinoma: Phase 3 KEYNOTE-630 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-138.