The combination of pembrolizumab and intratumoral SD-101 produced responses in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to phase 2 results published in Clinical Cancer Research.

SD-101 is a TLR9 agonist that stimulates plasmacytoid dendritic cells to release interferon-alpha and mature into efficient antigen-presenting cells, which enhances both innate and adaptive immune responses, the researchers explained.

In a phase 2 trial ( Identifier: NCT02521870), the researchers sought to determine if SD-101 can enhance the antitumor activity of pembrolizumab in patients with anti-PD-1/PD-L1-naïve recurrent/metastatic HNSCC.

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The study enrolled 51 patients. Their median age was 64.5 years (range, 38-93 years), and 78.4% were men. Most patients had oral (51.0%) or oropharyngeal (21.6%) primary tumors. Most patients had prior surgery (90.2%), radiation (80.3%), and received 1 or more prior lines of systemic therapy (76.5%).

All patients received pembrolizumab at 200 mg on day 1 and every 3 weeks until disease progression. There were 28 patients who had SD-101 injected in 1-4 lesions, at 2 mg per lesion. The other 23 patients received SD-101 at 8 mg injected into a single lesion. All patients received 2 courses of SD-101, with 9 weeks between courses. Each course consisted of 4 weekly doses and up to 7 additional doses every 3 weeks.


The median follow-up was 3.1 months for the 2 mg cohort and 5.6 months for the 8 mg cohort. The objective response rate (ORR) was 23.5% overall, 21.4% in the 2 mg cohort, and 26.1% in the 8 mg cohort.

Two patients had complete responses (both in the 2 mg cohort), and 10 had partial responses (6 in the 8 mg cohort). Responses were seen in injected and non-injected lesions. The median duration of response was 7.0 months overall, 7.0 months in the 2 mg cohort, and 5.7 months in the 8 mg cohort.

The ORR was 22.9% in patients with a PD-L1 combined positive score (CPS) of 1-19 and 26.7% in those with a CPS of 20 or higher. The ORR was 44% in patients with HPV-positive tumors and 12% in those with HPV-negative tumors.

The 9-month progression-free survival rate was 19.0% overall, 21.2% in the 2 mg cohort, and 17.4% in the 8 mg cohort. The 9-month overall survival rate was 64.7%, 79.9%, and 57.2%, respectively.

Adverse events (AEs) were seen in 100% of patients in the 8 mg cohort and 92.6% in the 2 mg cohort. Grade 3 or higher AEs were observed in 24% of patients. The most common of these were fatigue, myalgia, vomiting, constipation, increased gamma-glutamyl transferase, injection site erythema, and pyrexia.

Immune expression profiling at baseline and on-therapy biopsies from injected lesions suggested that adding SD-101 to pembrolizumab increased inflammatory gene expression and cellular immune responses. The researchers said these findings suggest that the treatment “may lead to biologically meaningful changes in the tumor microenvironment.”

Based on these results, the researchers proposed further testing of the combination in a phase 3 trial, particularly in patients with HPV-positive tumors.

Disclosures: This research was funded by Dynavax Technologies, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Cohen EEW, Nabell L, Wong DJ, et al. Intralesional SD-101 in combination with pembrolizumab in anti-PD-1 treatment naive head and neck squamous cell carcinoma: Results from a multicenter, phase 2 trial. Clin Cancer Res. Published online December 29, 2021. doi:10.1158/1078-0432.CCR-21-1411