European Society for Medical Oncology Congress
European Society for Medical Oncology Congress
October 22, 2018
3 min read

SD-101 plus pembrolizumab induces response in recurrent, metastatic head and neck cancer

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MUNICH — The addition of SD-101 to pembrolizumab induced a promising response rate among patients with recurrent or metastatic head and neck squamous cell carcinoma who had not received prior anti-PD-1 therapy, according to study results presented at European Society for Medical Oncology Congress.

The combination of SD-101 (Dynavax) and pembrolizumab (Keytruda, Merck) also appeared well tolerated.

“The combination treatment led to a response rate nearly double that of pembrolizumab [alone],” Ezra E.W. Cohen, MD, associate director of Moores Cancer Center at UC San Diego, told HemOnc Today. “The group of patients that the combination appeared most promising for in terms of efficacy was the PD-1 treatment-naive population.”

Prior studies showed a 14% overall response rate among patients with HNSCC treated with pembrolizumab.

SD-101 is a synthetic CpG-oligodeoxynucleotide toll-like receptor 9 agonist that stimulates dendritic cells to release interferon alpha and mature into antigen-presenting cells to activate T-cell antitumor responses, according to study background.

“SD-101 activates a different and complementary part of the immune system,” Cohen said. “Even when we looked at the pharmacodynamic data, we saw a Type 1 interferon response, which is exactly what SD-101 should do.

“This was accompanied by an infiltration of CD8-positive T cells into the tumor,” Cohen added. “With pembrolizumab onboard, the ability to activate those CD8-positive T cells appears to result in a response rate that is double that of pembrolizumab alone.”

The phase 1b/phase 2 SYNERGY-001 trial assessed the safety and preliminary efficacy of intratumoral SD-101 in combination with anti-PD-1 therapy pembrolizumab for patients with recurrent or metastatic head and neck cancer.

One of two phase 2 expansion cohorts included 26 patients (median age, 65 years) naive to anti-PD-1/anti-PD-L1 treatment.

Most patients were men (91%), had an ECOG performance status of 0 or 1 (96%) and had received a median one prior line of therapy in the metastatic setting (range, 0 to 2).

They received 8 mg SD-101 injected in a single tumor lesion (weekly for four doses, followed by every 3 weeks for seven more doses). They also received 200 mg pembrolizumab via IV every 3 weeks.

Researchers used RECIST v1.1/irRECIST criteria to assess responses, and they reported responses for a modified intention-to-treat population that excluded patients who had not yet reached their first CT scan.

At the time of analysis, patients had received a median five doses (range, 1-16) of SD-101.

Researchers reported a 30.4% overall response rate in the modified intention-to-treat population (n = 23). Responses occurred among patients with PD-L1-positive tumors, as well as PD-L1-negative tumors.


Seven patients achieved partial response, and five of these partial responses remained ongoing at the time of analysis (duration range, 1 week to 27 weeks).

Three patients demonstrated stable disease.

Ten patients experienced disease progression. Three patients discontinued treatment due to clinical progression before their initial CT scan.

Researchers observed tumor shrinkage greater than 30% among eight of 18 (n = 44.4) injected lesions, as well as eight of 14 (57.1%) noninjected lesions.

Fewer than one-third (28%) of patients experienced grade 3 or higher treatment-related adverse events; these included flu-like symptoms, myalgia, headache, fatigue, and injection site pain and swelling.

No new safety signals emerged with pembrolizumab, and investigators reported no increased incidence or severity of adverse events compared with pembrolizumab monotherapy. Sixteen percent of patients experienced immune-related adverse events.

Fifteen patients required treatment interruption. These included 10 interruptions due to disease progression and two due to adverse events. One patient withdrew consent and one person died due to a nontreatment-related cause. The reason for the other interruption was not specified.

“We expect the trial to be complete by the end of this year or early 2019,” Cohen told HemOnc Today. “Beyond this, we will allow the data to mature a bit and ensure that we are, in fact, seeing the promising activity that we think we are seeing. We will then hopefully move SD-101 into larger randomized studies that truly demonstrate that this combination is better than single-agent pembrolizumab or better than current standards of care in head and neck cancer.” – by Jennifer Southall


Cohen EEW, et al. 1050_PD. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: Dynavax Technologies Corporation provided funding for this study. Cohen reports consultant or advisory roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Merck, and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.