Pembrolizumab Combo Shows Positive Response Potential in Melanoma

New data presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting show that a new combination could provide long-term, systemic responses in patients with advanced melanoma.

The poster presentation, presented by Dynavax Technologies Corporation, features results from the Phase 1b/2 MEL-01 (KEYNOTE-184) study. The durability of response data suggest that the company’s intratumoral Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide, SD-101, in combination with pembrolizumab (Keytruda), resulted in an ongoing response rate of 86% (n=6) at a median follow-up of 18 months for patients who were naïve to anti-PD-1/L1 treatment.¹

The dose-escalation and expansion study of SD-101 in combination with Keytrude includes patients with histologically or cytologically confirmed unresectable Stage IIIc/IV melanoma. Safety of intratumoral SD-101 in combination with Keytruda served as the primary endpoint.

“We are encouraged by the review of the safety, durability, and anti-tumor response in this initial group of patients,” said Eddie Gray, Chief Executive Officer of Dynavax in a press release. “These preliminary results suggest that not only is this combination generating immune activity in the injected tumors, but that we can also induce an immune response to tumors at distant sites. These findings, coupled with our recently reported head and neck data provide further support for our plans to expand our clinical program into multiple tumor types in combination with a range of modalities.”²

Median progression-free survival (PFS), duration of response, and overall survival (OS) in naïve patients have not yet been reached.

In the study, partial or stable disease response for at least 10.5 months was achieved by 2 of 12 evaluable patients with progressive disease on prior anti-PD-1/L1 monotherapy, and the drug was well tolerated and exhibited no increase in the frequency of immune-related adverse events (AEs) over individual monotherapies. There was additionally no evidence of a unique safety signal.

The most common treatment-related AEs were injection site reactions and transient mild-to-moderate flu-like symptoms, including fever, chills and myalgia. Responses were observed in the injected lesion and in distant lesions, including visceral metastases in the lung.

To further evaluate the safety and activity of SD-101, Dynavax is also evaluating the drug in a Phase 2 study in combination with pembrolizumab in patients with head and neck squamous cell cancer (HNSCC). The combination demonstrated promising antitumor activity with an acceptable safety profile in anti-PD-1/L1 naïve recurrent unresectable or metastatic HNSCC.

In both studies, it was concluded that combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade has the potential to increase clinical efficacy with insignificant additional toxicity comparative to PD-1 blockade alone.³

References:

1. Ribas A, Medina T, Kummar S, et al. Durability of Responses to SD-101 in Combination with Pembrolizumab in Advanced Metastatic Melanoma: Results of a Phase 1b, Multicenter Study. Presented at: 2018 American Association for Cancer Research (AACR) Annual Meeting; April 14-18, 2018; Chicago, IL. Abstract CT139.
2. Dynavax Provides New Durability of Response Data for SD-101 in Combination with KEYTRUDA® (pembrolizumab) in Melanoma at the 2018 American Association for Cancer Research Annual Meeting. Dynavax Technologies Corporation. http://www.globenewswire.com/news-release/2018/04/17/1480247/0/en/Dynavax-Provides-New-Durability-of-Response-Data-for-SD-101-in-Combination-with-KEYTRUDA-pembrolizumab-in-Melanoma-at-the-2018-American-Association-for-Cancer-Research-Annual-Meeti.html. Accessed April 18, 2018.
3. Cohen E, Milhem M, Ribas A, et al. 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. Presented at: 2018 American Association for Cancer Research (AACR) Annual Meeting; April 14-18, 2018; Chicago, IL. Abstract CT098.