Vidutolimad Plus Pembrolizumab in PD-1 Refractory Melanoma

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The addition of vidutolimod to pembrolizumab could help overcome resistance to immune checkpoint inhibition in patients with metastatic or unresectable cutaneous melanoma, according to data presented by John M. Kirkwood, MD, and colleagues at the Society for Immunotherapy of Cancer (SITC) 2021 Annual Meeting (Abstract 950).

Results from a phase Ib study showed that treatment with vidutolimod plus pembrolizumab demonstrated promising clinical antitumor activity in patients with PD-1 blockade–refractory melanoma. Authors of the study reported an overall response rate of 23.5%; 7.1% of patients achieved a complete response. Responses were also durable, with a median duration of response of more than 2 years in responders.

“Tumor regression was seen both in injected and in noninjected lesions, supporting a systemic immune effect of vidutolimod,” said lead study author Dr. Kirkwood, Professor of Medicine, Dermatology, and Clinical and Translational Science at the University of Pittsburgh School of Medicine. “Vidutolimod also demonstrated single-agent activity, but the substantially longer duration of response with pembrolizumab provides strong rationale for further development of vidutolimod in combination with PD-1 blockade.”

Vidutolimod also demonstrated single-agent activity, but the substantially longer duration of response with pembrolizumab provides strong rationale for further development of vidutolimod in combination with PD-1 blockade.
— John M. Kirkwood, MD

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Vidutolimod is a first-in-class immunostimulatory noninfectious viral particle that contains a CpG-A toll-like receptor 9 agonist and is delivered as a biologic virus-like particle.

Phase Ib Trial

The objective of this two-part, open-label, multicenter phase Ib study was to assess the safety and antitumor activity of vidutolimod alone and in combination with pembrolizumab in patients with advanced melanoma and prior disease progression on anti–PD-1 therapy.

Dr. Kirkwood and colleagues enrolled a total of 159 patients in part 1 and 40 patients in part 2 of the trial. The demographics and baseline characteristics were similar across groups.

As Dr. Kirkwood reported, antitumor activity was observed with vidutolimod in combination and as monotherapy. In 98 patients receiving vidutolimod plus pembrolizumab, the best overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was 23.5%. In the 40 patients who received vidutolimod monotherapy, the best overall response rate per RECIST criteria was 20%.

The combination of vidutolimod and pembrolizumab also resulted in durable responses, with a median duration of response of 25.2 months. Conversely, vidutolimod monotherapy had a median duration of only 5.6 months.

Similar responses were observed across baseline characteristics, including ECOG performance status 0 or 1 and BRAF V600E/K–mutated disease vs wild-type status. Responses were also seen regardless of the number of prior therapies, said Dr. Kirkwood, including in patients with more than four prior therapies.

Similar responses were observed in vidutolimod-injected and -noninjected target lesions, including visceral metastases.

Dr. Kirkwood also reported a manageable safety profile for vidutolimod, with most treatment-related adverse events being grade 1 or 2. Grade 3 and 4 treatment-related adverse events occurred in 37.1% of patients treated with vidutolimod plus pembrolizumab and in 22.5% of patients treated with vidutolimod monotherapy. No treatment-related deaths occurred.

Clinical studies to confirm the efficacy of vidutolimod with PD-1 blockade in patients with previously untreated advanced melanoma, as well as those with PD-1–refractory melanoma, are ongoing. Based upon these results, the 10-mg dose and schedule A were selected as the recommended phase II doses for vidutolimod.

Disclosure: This research was supported by Checkmate Pharmaceuticals.  


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.