Phase I study to evaluate the safety and efficacy of MEDI4736 in combination with tremelimumab in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

TPS3090 Background: Despite advances in the treatment of SCCHN, the outlook for patients (pts) with R/M disease remains poor. Development of immunotherapies to treat this disease may hold promise. High mutational burden due to tobacco and expression of human papilloma virus (HPV)-associated viral antigens is linked to immunogenicity in SCCHN tumors. Despite this immunogenicity, tumors can evade immune detection by exploiting inhibitory checkpoints. PD-L1 is up-regulated on SCCHN tumors and is associated with antitumor T-cell response inhibition. MEDI4736 (M), a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity, has shown a manageable safety profile and promising antitumor activity in R/M SCCHN (ORR 24% in PD-L1+ pts, phase I)(Fury M, et al. Poster presented at ESMO 2014, 988PD). Tremelimumab (T), a selective human IgG2 mAb inhibitor of CTLA-4, has also shown antitumor activity in several tumor types (Tarhini AA. Immunotherapy 2013;5:215–29). Preclinical data sugg...