Iris Gluck

Second-line treatment options for advanced head and neck squamous cell carcinoma (HNSCC) are limited. The phase Ib KEYNOTE-012 study evaluated the safety and the efficacy of pembrolizumab for the treatment of HNSCC after long-term follow-up. Multi-centre, non-randomised trial included two HNSCC cohorts (initial and expansion) in which 192 patients were eligible. Patients received pembrolizumab 10 mg/kg every 2 weeks (initial cohort; N = 60) or 200 mg every 3 weeks (expansion cohort; N = 132). Co-primary endpoints were safety and overall response rate (ORR; RECIST v1.1; central imaging vendor review). Median follow-up was 9 months (range, 0.2–32). Treatment-related adverse events (AEs) of any grade and grade 3/4 occurred in 123 (64%) and 24 (13%) patients, respectively. No deaths were attributed to treatment-related AEs. ORR was 18% (34/192; 95% CI, 13–24%). Median response duration was not reached (range, 2+ to 30+ months); 85% of responses lasted ≥6 months. Overall survival at 12 months was 38%. Some patients received 2 years of treatment and the responses were ongoing for more than 30 months; the durable anti-tumour activity and tolerable safety profile, observed with long-term follow-up, support the use of pembrolizumab as a treatment for recurrent/metastatic HNSCC.

6011 Background: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. MK-3475 is a highly selective, humanized IgG4/kappa isotype mAb designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, to reactivate the immune system to eradicate the host tumor. Methods: Pts with recurrent/metastatic H/N cancer were enrolled in this multi-center, non-randomized trial in two cohorts (HPV and non-HPV associated). Pts were prescreened for PD-L1 expression by immunohistochemistry (22C3), and if positive allowed to proceed with treatment of single agent MK-3475 given intravenously at 10 mg/kg every 2 wks. Primary objectives are to determine (1) safety and tolerability and (2) anti-tumor activity of MK-3475 assessed by RECIST 1.1. Secondary objectives include progression-free survival, overall survival and response duration. Results: All results are based on preliminary, unaudited data as of Jan. 27, 2014. 77.9% of patients expressed PD-L1, defined as ≥1% of stained cells in the tumor microenvironment (Table). Of 60 patients (11 female, 49 male) enrolled in the study, 19 had an ECOG status of 0, and 40 had an ECOG status of 1 (1 unknown); 23 were HPV+ and 37 were HPV-; 9 had no prior systemic treatment, 10 had 1, 16 had 2, 13 had 3, and 7 had ≥4 prior regimens of treatment (5 unknown). Of the patients treated with MK-3475, 78.3% experienced ≥1 AE, and 46.7% reported a drug-related (DR) AE. The most common DR AEs reported were pruritis (6, 10%), fatigue (4, 7%), rash (4, 7%), and diarrhea (3, 5%). At least one Grade 3-5 AE was reported in 55.0% of patients, with 13.3% reporting a DR Gr 3-5 AE. Grade 3-5 AEs considered DR were hyponatremia, lymphopenia, rash, diarrhea, musculoskeletal pain, abscess (neck), and atrial fibrillation. Tumor shrinkage was observed in several patients, but protocol-specified efficacy analyses are not yet available. Conclusions: To date, treatment with MK-3475 has been well tolerated overall, with few serious DR AEs. Protocol-specified efficacy analyses are not yet available. Clinical trial information: NCT01848834.PD-L1 staining in tumors of screened patients (n=104). Staining (%) 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 n 50 8 9 3 2 2 4 3 2 21