Abstract 7518: Neoadjuvant-adjuvant pembrolizumab in resectable advanced basal cell carcinoma of the head and neck: An open-label, single-arm, phase 1b trial

Abstract Introduction: BCC is a common form of skin cancer that shares treatment-related aspects with the more well-studied skin malignancy, melanoma, including sensitivity to anti-PD-1/PD-L1 immunotherapy. However, despite major advances in peri-operative immunotherapy for melanoma, little is known regarding these strategies in BCC. This phase 1B, single-arm study evaluated neoadjuvant-adjuvant treatment with pembrolizumab (PEMBRO) together with standard of care (SOC) resection in advanced BCC of the head and neck. Methods: Eligible patients had resectable, locally advanced BCC of the head and neck, defined by at least one of the following high-risk characteristics: a measurement of ≥ 20 mm, indication for post-operative radiation, or perineural invasion (PNI) in multiple nerves. Patients were naive to hedgehog inhibitors (HHI) and had an ECOG of 0 or 1. All patients received IV PEMBRO at a dose of 200 mg every 3 weeks for a total of 4 cycles, then within 4 weeks underwent a SOC resection followed by adjuvant PEMBRO until a total of 17 cycles was completed. After the 30-day post treatment safety follow-up visit, patients were followed for up to 5 years post-operatively. The primary endpoint was pathological response rate. Secondary endpoints included RECIST response by radiographic or physical exam, adverse events (AE), and recurrence-free survival (RFS). Results: 13 patients were enrolled in the trial from July 2020 to May 2023, and received at least one dose of PEMBRO. Two patients withdrew from the trial after one dose of PEMBRO, one following treatment-related G3 hepatitis and a second due to an unrelated medical complication (cholecystitis). Out of 11 patients undergoing surgical resection, 10 patients received 4 out of 4 and 1 patient received 3 out of 4 planned cycles of neoadjuvant PEMBRO (investigator preference without new related AE). Pathological complete response (pCR) was observed in 3 patients (23%). For those with RECIST measurable disease, 2 patients demonstrated a complete response (CR), 1 patient a partial response (PR), and 5 patients showed stable disease (SD). Two patients had progressive disease (PD). One patient with a complete pathologic response had a discordant RECIST response with PD noted radiographically. All 13 patients experienced at least one AE of G1 or 2. The highest grade of related AEs were noted in 2 patients with grade 3 hepatitis and pruritus respectively that resolved with supportive therapy. As of November 2023, the median follow-up time is 17.6 months with no recurrences noted. Conclusions: Neoadjuvant-adjuvant PEMBRO shows promising efficacy and an acceptable safety profile in resectable advanced BCC of the head and neck. Given these positive results and the healthcare burden BCC accounts for, these findings warrant further study. Citation Format: Grace M. Jones, James Isaacs, Lucy Boyce Kennedy, Jennifer Ko, Allison Vidimos, Alok Vij, Christine Poblete-Lopez, Jennifer Lucas, Yee Peng Phoon, Melissa McEnery-Stonelake, Jon Meine, Thach-Giao Truong, Pauline Funchain, Brian Gastman. Neoadjuvant-adjuvant pembrolizumab in resectable advanced basal cell carcinoma of the head and neck: An open-label, single-arm, phase 1b trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7518.