Neoadjuvant Vidutolimod Plus Pembrolizumab Displays High pCR Rates in Resectable Melanoma

Neoadjuvant vidutolimod in combination with pembrolizumab (Keytruda) demonstrated encouraging efficacy in patients with stage III resectable melanoma, according to data from the phase 2 ECOG-ACRIN EA6194 trial (NCT04708418).1

At the January 28, 2025, data cutoff, findings presented during the 2025 ASCO Annual Meeting revealed that efficacy-evaluable patients who received the combination and underwent definitive surgery (n = 27) achieved a pathologic complete response (pCR) rate of 74% (95% CI, 54%-89%), including a near-pCR rate of 7.5%. Patients who received pembrolizumab alone and underwent definitive surgery (n = 25) achieved a pCR rate of 56% (95% CI, 35%-76%) and a near-pCR rate of 12%. The major pathologic response rates in the combination and monotherapy arms were 81% (95% CI, 62%-94%) and 68% (95% CI, 46%-85%), respectively. The median time to surgery from random assignment in both arms was 2.5 months.

“The study met its primary end point of improving pCR [rate],” Ahmad A. Tarhini, MD, PhD, said in an interview with OncLive®. “The [findings in the combination arm] compared favorably with the control arm and with historical controls.”

Tarhini is a tenured senior member in the Department of Cutaneous Oncology and Department of Immunology, the director of cutaneous clinical and translational research, and the leader of the Neoadjuvant and Adjuvant Translational Science Program at Moffitt Cancer Center, as well as a professor of oncologic sciences at the University of South Florida Morsani College of Medicine in Tampa, Florida.

Unpacking the Study Design and Baseline Characteristics

ECOG-ACRIN EA6194 enrolled patients with American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th Edition clinical stage IIIB, IIIC, or IIID resectable macroscopic melanoma.1 Patients needed to be at least 18 years old, have an ECOG performance status of 0 or 1, have injectable and measurable disease per RECIST 1.1 criteria, adequate laboratory values, and have not receive prior systemic therapy for melanoma, including an anti–PD-1, anti–PD-L1, anti–CTLA-4 or BRAF/MEK inhibitor combination, and/or a TLR-9 agonist.2

Eligible patients were randomly assigned 1:1 to arm A or arm B. In arm A, patients received neoadjuvant pembrolizumab at 200 mg every 3 weeks for 3 cycles.1 In arm B, patients received pembrolizumab via the same dosing schedule in combination with subcutaneous vidutolimod at 5 mg for 1 cycle, followed by a 10-mg dose every week for 6 cycles. All patients underwent surgery 9 to 11 weeks after day 1 of cycle 1. Patients in both arms received adjuvant pembrolizumab at 400 mg every 6 weeks for 8 cycles.

The primary end point was the pCR rate. Secondary end points included radiographic response rate, relapse-free survival, overall survival, event-free survival (EFS) and the incidence of adverse effects (AEs).1,2

At baseline, the median age in the overall patient population (n = 57) was 64 years (range, 26-88).1 All patients were White and had cutaneous primary disease. Most patients were male (67%) and had an ECOG performance status of 0 (81%). Patients had clinical stage IIIB (40%), IIIC (56%), or IIID (3.5%) disease.

Further Efficacy Data and Safety Results

At a median follow-up of 19 months (range, 2-36), the 1-year EFS rates among all enrolled patients were 89% (95% CI, 78%-100%) and 75% (95% CI, 59%-91%) in arm B and arm A, respectively. Additionally, the respective ORRs were 43% and 50%, including complete response rates of 7% and 4%, respectively.

In terms of safety, any-grade AEs occurred at rates of 86% and 100% in arms A (n = 28) and B (n = 28), respectively. The most common any-grade AEs in arm A included fatigue (39%), maculopapular rash (32%), and increased alanine transaminase/aspartate transaminase (21%). Common any-grade AEs in arm B included fatigue (68%), cytokine release syndrome (39%), and increased alanine transaminase/aspartate transaminase (39%).

Grade 3 or 4 AEs were reported in 25% of patients in arm A and 29% in arm B. No grade 5 AEs were observed.

“The results were very encouraging and therefore have justified moving forward with a definitive phase 3 clinical trial,” Tarhini said. “In addition, we have banked extensive biospecimens in the context of the study from consenting patients and currently have a comprehensive biomarker and mechanistic plan that is ongoing.”

Disclosures: Tarhini has consulting or advisory roles with AstraZeneca, Bayer, BioNTech, Bristol-Myers Squibb, Clinigen, ConcertAI, Eisai, Genentech/Roche, Instil Bio, Merck, Nested, Novartis, Partner Therapeutics, and Sanofi/Regeneron. He has also received research funding from Acrotech Biopharma, Agenus, Bristol-Myers Squibb, Clinigen, Genentech/Roche, InflaRx, Merck, OncoSec, Pfizer, Sanofi/Regeneron, and Scholar Rock.

References

1. Tarhini A, Lee S, Davar D, et al. A phase II randomized study of neoadjuvant pembrolizumab (P) alone or in combination with vidutolimod (V) in high-risk resectable melanoma: ECOG-ACRIN EA6194. J Clin Oncol. 2025;43(suppl 17):LBA9505. doi:10.1200/JCO.2025.43.17_suppl.LBA9505
2. A study evaluating whether pembrolizumab alone or in combination with CMP-001 improves efficacy of treatment in patients with operable melanoma. ClinicalTrials.gov. Updated August 5, 2025. Accessed August 12, 2025. https://www.clinicaltrials.gov/study/NCT04708418