Abstract PO-009: Phase 3 KEYNOTE-630 study of adjuvant pembrolizumab in high-risk locally advanced cutaneous squamous cell carcinoma
Authors: Schenker Michael , Klochikhin Mikhail , Kirtbaya Dmitry , Mortier Laurent , Gschnell Martin , Robert Caroline , Meyer Nicolas , Flatz Lukas , Dalle Stephane , Beylot-Barry Marie , Eigentler Thomas , Silverman Rachel Kloss , Gumuscu Burak , Yuan Jianda , Bratland Aase 
Published: September 2023

Abstract
Introduction: Among patients with high-risk locally advanced (LA) cutaneous squamous cell carcinoma (cSCC), approximately 20% experience local disease recurrence within 5 years after standard-of-care surgical resection and adjuvant radiotherapy. Better treatment options are needed for patients who experience recurrence after surgery. The PD-1 inhibitors pembrolizumab (pembro) and cemiplimab have shown durable antitumor activity in advanced metastatic cSCC. The randomized, double-blind, placebo-controlled, phase 3 KEYNOTE-630 (NCT03833167) trial will be conducted to evaluate adjuvant pembro in patients with resectable, high-risk, LA cSCC. Materials and Methods: Eligible patients will have histologically confirmed LA cSCC as the primary site of malignancy and have undergone complete macroscopic resection of all disease with ≥1 high-risk feature: histologically involved nodal disease with extracapsular extension, with ≥1 lymph node &gt;2 cm in diameter or ≥2 lymph nodes involved; any gross cortical bone, skull base, and/or skull base foramen invasion; any index tumor with ≥2 of the following: tumor ≥4 cm with &gt;6-mm depth or invasion beyond subcutaneous fat, multifocal perineural invasion for nerves &lt;0.1 mm in diameter (≥3 foci) or any involved nerve ≥0.1 mm in diameter, poor differentiation and/or sarcomatoid and/or spindle cell histology, recurrent disease (recurrence within 3 years in the previously treated area), or satellite lesions and/or in-transit metastases, lymphatic or vascular involvement. Patients must have received adequate postoperative dose of hypofractionated or conventional radiotherapy, including a BED EQD2 &gt;48 Gy, have ECOG PS of 0 or 1, and completed adjuvant radiotherapy ≥4 and ≤16 weeks from randomization. Patients are required to provide tumor tissue for PD-L1 testing and have an ECOG PS of 0 or 1. Approximately 570 patients will be randomly assigned 1:1 to pembro 400 mg IV every 6 weeks or placebo for approximately 1 year (≤9 cycles). Stratification factors are extracapsular extension, cortical bone invasion, and prior systemic therapy (all, yes vs no). Patients receiving placebo may be eligible to cross over to receive pembro (≤18 cycles) if first biopsy-proven recurrence occurs within 5 years. In the pembro arm, eligible patients may receive pembro retreatment for up to 18 cycles. The primary end point is recurrence-free survival per investigator assessment with biopsy confirmation and secondary end points include overall survival, health-related quality of life, and safety. Computed tomography/magnetic resonance imaging of disease-involved areas and associated lymph nodes will be performed at screening and every 12 weeks until the end of year 2, then every 6 months until the end of 5 years. Adverse events will be monitored throughout the study and for 30 days after treatment end and graded per NCI CTCAE v4.0. Results: Recruitment is underway at sites in Asia, Australia, Europe, and North and South America. Conclusions: Results of KEYNOTE-630 will elucidate the role of adjuvant pembro in patients with high-risk, LA cSCC.
Citation Format: Michael Schenker, Mikhail Klochikhin, Dmitry Kirtbaya, Laurent Mortier, Martin Gschnell, Caroline Robert, Nicolas Meyer, Lukas Flatz, Stephane Dalle, Marie Beylot-Barry, Thomas Eigentler, Rachel Kloss Silverman, Burak Gumuscu, Jianda Yuan, Aase Bratland. Phase 3 KEYNOTE-630 study of adjuvant pembrolizumab in high-risk locally advanced cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-009.