Ahmad Tarhini, MD, PhD, Moffitt Cancer Center and Research Institute, Tampa, Florida, discusses results from the phase 2 EA6194 study which assessed pembrolizumab plus vidutolimod vs pembrolizumab alone in patients with high-risk resectable melanoma.

Study findings show that pembrolizumab plus vidutolimod exhibited promising efficacy and safety in this patient population. 

Dr Tarhini presented these results at the 2025 ASCO Annual Meeting in Chicago, Illinois. 

Transcript:

My name is Ahmad Tarhini, professor and senior member in cutaneous oncology and immunology at Moffitt Cancer Center in Tampa, Florida. I'm the chair of the EA6194 clinical trial which is an NCI sponsored randomized phase 2 study conducted by ECOG-ACRIN. 

In this study, we targeted a patient population with locoregionally advanced melanoma. These are patients with bulky disease at high-risk for recurrence and death after definitive surgery. There have been important advances recently, but there continues to be a need for us to improve the clinical efficacy and minimizing the systemic toxicity in managing these patients. EA6194 tested an important and novel combination of anti-PD1 monotherapy in addition to vidutolimod, which is a TLR9 nine agonist. TLR9 is an endosomal receptor which is expressed by B cells and plasmacytoid dendritic cells and the activation of TLR9 leads to the stimulation of type I interferon, which leads to the stimulation induction of innate and adaptive antitumor immune responses. 

The patients were allocated 1-to-1 to each arm of the study, treated for about 12 weeks, and then we had definitive surgery at about 9 to 11 weeks. All patients then moved on to have anti-PD1 monotherapy as adjuvant therapy. The primary end point was the pathologic complete response. We also looked at other efficacy and safety end points including major pathologic response, which is complete or near complete pathologic response, and event free survival, which takes into account the events of progression, recurrence after surgery, or death from disease or treatment. 

The study was positive as designed, meaning the combination arm demonstrated in very encouraging efficacy outcomes, including a pathologic complete response rate of 71%. The major pathologic response rate was 79%, and the 1-year event-free survival rate was 89%. All of these compared very favorably to the control arm of anti-PD1 as monotherapy as well as to historical controls. Therefore, the data overall was positive and has justified moving forward with definitive testing in the form of a phase 3 clinical trial. In addition, we have a comprehensive biomarker and mechanistic analysis that is currently ongoing, this is also funded by the NCI and in collaboration with the CMAC and CIDC laboratories.

Source: 

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. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA9505