Background and Objectives: SD-101 is a synthetic CpG-ODN agonist of TLR9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells to activate T cell anti-tumor responses. Pembrolizumab is a PD-1 inhibitor that has demonstrated activity in HNSCC with ORR of 14%. Study DV3-MEL-01 (NCT02521870) assesses the safety and preliminary efficacy of SD-101 in combination with pembrolizumab in patients with recurrent or metastatic HNSCC.

Methods: In phase 2 expansion cohort for anti-PD-1 treatment naïve HNSCC patients, SD-101 was injected in a single tumor lesion (weekly x 4 doses then every 3 weeks x 7 doses) at 8 mg and pembrolizumab was administered intravenously at 200 mg every 3 weeks. Responses are assessed per investigator using RECIST v1.1/irRECIST.

Preliminary Data and Results: 16 anti-PD-1 treatment naïve HNSCC patients are enrolled to date: median age 65 y/o, male 94%, ECOG PS1 63%, median prior lines of therapy 1. SD-101 safety profile consists of flu-like symptoms and injection-site reactions. Grade≥3 treatment-related AEs observed to date included influenza-like symptoms, myalgia, headache, injection site pain and swelling, and fatigue with each of the toxicities occurring in 1 patient (6.7%). No increase in frequency of known pembrolizumab immune-related AEs has been observed to date. ORR in evaluable pts (n=10) was 40% (4 PRs; 1 SD, 5 PDs with 1 still on treatment). The duration of response will be characterized when follow-up data become more mature.

Conclusions: In anti-PD-1 treatment naïve HNSCC patients, SD-101 in combination with pembrolizumab showed a promising response rate and has been well tolerated. Full accrual of subjects in this cohort is ongoing.

Citation Format: Ezra Cohen, Sarwan Bishnoi, Douglas E. Laux, Deborah Wong, Asim Amin, Lisle Nabell, Emmett V. Schmidt, Biao Xing, Abraham C. Leung, Robert Janssen. Phase Ib/II, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT098.