e21056 Background: High risk cutaneous squamous cell cancer of the head and neck (cSCC-HN) have suboptimal outcomes with surgery and postoperative radiation. We report preliminary safety outcomes of a phase II study (NCT03057613) exploring the safety and efficacy of the addition of Pembrolizumab to postoperative IMRT. Methods: Patients with cSCC-HN were eligible for this IRB approved study if they had resection of all gross disease and demonstrated (a) invasion of the skeleton or skull base; (b) node positive disease; (c) or a tumor > 2cm with ≥1 of the following risk factors: recurrent disease, perineural invasion, lymphovascular space invasion, poorly differentiated, positive margins, satellitosis or in-transit metastases. Immune competent pts and those with CLL were eligible. This study aimed to accrue 34 evaluable patients to assess a primary safety endpoint of dose limiting toxicity (DLT) defined as any grade ≥3 toxicity at least possibly related to the immunotherapy. Assuming toxicity of < 20% is acceptable and > 40% is unacceptable, if ≥11 of 34 (32%) patients experienced a DLT, the regimen would be considered unsafe. Results: Of 15 pts already enrolled on this study, 11 have completed the protocol treatment. There were no DLTs observed to date. Grade 2 immune related toxicity was seen in two patients, one with bullous pemphigoid and another with lymphopenia and peripheral neuropathy and weakness in his hands in the setting of a prior cervical spine injury. Both responded to steroids and recovered completely. Based on this initial cohort, the 95% confidence intervals (CI) on DLTs for the entire cohort is 0-28%. Using the most conservative CI of 28%, the likelihood of 11 of the remaining 23 patients experiencing a DLT is 3.4%. Assuming a CI of 20%, the risk is 0.3%. None of the 11 pts who have completed protocol therapy have experienced a recurrence. Conclusions: The addition of Pembrolizumab to postoperative IMRT in high risk cSCC-HN is safe and will be studied in a randomized phase III adjuvant study (Keynote 630). This phase II study will continue to enroll CLL patients to assess safety and efficacy signals in this unique higher risk population. Clinical trial information: NCT03057613.
Adjuvant radiotherapy in high-risk cutaneous squamous cell cancer of the head and neck in immunosuppressed patients