Abstract CT163: KEYNOTE-412: Pembrolizumab plus chemoradiation vs chemoradiation alone for locally advanced head and neck squamous cell carcinoma

Background: Chemoradiation (CRT) with cisplatin is the standard of care for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) not treated by surgery. Preclinical data in murine cancer models show improved tumor growth control and survival when radiation therapy (RT) is combined with a PD-1 inhibitor. Pembrolizumab is effective for treatment of recurrent/metastatic HNSCC, and initial results from a phase 1b study suggest that pembrolizumab plus CRT is tolerable in patients with LA-HNSCC. KEYNOTE-412 (NCT03040999) is a phase 3, randomized, placebo-controlled, double-blind trial to determine the efficacy and safety of pembrolizumab given with CRT and as maintenance therapy versus placebo plus CRT in LA-HNSCC. Trial design: Patients will be randomly assigned (1:1) to receive pembrolizumab 200 mg every 3 weeks plus cisplatin-based CRT or placebo plus cisplatin-based CRT. Treatment will be stratified by RT regimen (accelerated RT [56-70 Gy, 6 fractions/week for 6 weeks] or standard RT [56-70 Gy, 5 fractions/week for 7 weeks]), tumor site/p16 status (oropharynx p16 positive vs p16 negative or larynx/hypopharynx/oral cavity), and disease stage (III vs IV). A priming dose of pembrolizumab or placebo will be given 1 week before CRT, followed by 2 doses during CRT and an additional 14 doses after CRT, for a total of 17 pembrolizumab or placebo infusions. Eligibility criteria include age ≥18 years; newly diagnosed, treatment-naive, oropharyngeal p16 positive (any T4 or N3), oropharyngeal p16 negative (any T3-T4 or N2a-N3), or larynx/hypopharynx/oral cavity (any T3-T4 or N2a-N3) SCC; evaluable tumor burden (RECIST v1.1); and ECOG performance status 0-1. Treatment will be discontinued at centrally confirmed disease progression, unacceptable toxicity, or patient/physician decision to withdraw. Response will be assessed by computed tomography or magnetic resonance imaging 12 weeks after CRT, every 3 months for 3 years, then every 6 months for years 4 and 5. Patients will be evaluated to determine the necessity of neck dissection 12 weeks after completion of CRT; neck dissection will be recommended in cases of persistent disease. After a patient experiences disease progression or starts new anticancer therapy, the patient will begin survival follow-up and will be contacted every 3 months during years 1 through 3 and every 6 months during years 4 and 5 until death, withdrawal of consent, or the end of the study, whichever occurs first. Safety w