3560 - Phase 1b/2, 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)

Background

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 with demonstrated activity in HNSCC with an ORR of 14%. Study DV3-MEL-01 (SYNERGY-001) assesses safety and preliminary efficacy of SD-101 in combination with pembrolizumab in patients with recurrent or metastatic HNSCC.

Methods

In a phase 2 expansion cohort for anti-PD-1/PD-L1 treatment naïve recurrent and/or metastatic HNSCC patients, SD-101 was injected in a single tumor lesion (Weekly x 4 doses then Q3W x 7 doses) at 8 mg and pembrolizumab was administered IV (200 mg Q3W). Responses are assessed per investigator using RECIST v1.1/irRECIST and reported for the modified ITT (mITT) population that excludes patients on study who have not yet reached the first CT scan.

Results

26 patients are enrolled to date: median age 65 y/o; male 91%; ECOG PS 0-1 (23%/73%); median prior lines of therapy in metastatic setting 1 (0 to 2); median treatment duration is 9 weeks (1 to 45). 15 patients interrupted treatment: 10 PD, 2 AEs, 1 withdrew consent, 1 death not treatment related, 1 other. SD-101 safety profile with a median of 5 doses (1.0 to 16.0) consists of flu-like symptoms and injection-site reactions. 28% Grade≥3 SD-101 treatment-related AEs including influenza-like symptoms, myalgia, headache, injection site pain and swelling, and fatigue. No increase in frequency of known pembrolizumab immune-related AEs (16%) and no new safety signal. ORR in mITT (n = 23) was 30.4% (7 PR; 3 SD, 10 PD, 3 discontinued due to clinical progression before first scan). Tumor shrinkage > 30% was seen in injected (8/18: 44.4%) and non-injected lesions (8/14: 57.1%). Five of the 7 PR are ongoing, (1 to 27 weeks).

Conclusions

In anti-PD-1 treatment naïve recurrent and/or metastatic HNSCC patients, SD-101 in combination with pembrolizumab showed a promising response rate and has been well tolerated. SD-101 appears to enhance the systemic effect of anti-PD-1 blockade.

Clinical trial identification

NCT02521870.

Legal entity responsible for the study

Dynavax Technologies Corporation.

Funding

Dynavax Technologies Corporation.

Editorial Acknowledgement

Disclosure

E.E.W. Cohen: Consulting or advisory role: Eisai, Pfizer, Merck, AstraZeneca, Bristol-Myers Squibb. A. Algazi: Research funding to institution: BMS, Merck, AstraZeneca, Medimmune, Acerta, Oncosec, Idera, Incyte, and Genentech; Unpaid advisor: Oncosec, Valitor. A. Amin: Honoraria from speaker’s bureau: Merck & Co. M. Chisamore: Employee: Merck & Co. E. Gamelin: Employee: Dynavax Technologies. R. Janssen: Employee: Dynavax Technologies; Stock holder: Dynavax Technologies, Merck. All other authors have declared no conflicts of interest.