EA6194 – A Phase II Randomized Study of Neoadjuvant Pembrolizumab Alone or in Combination with CMP-001 in Patients with Operable Melanoma: Efficacy and Biomarker Study

Patients with locally or regionally advanced melanoma who are at high risk of recurrence need better treatment options and improved outcomes, including reduced surgical morbidity. The use of novel immunotherapy and targeted therapy, alone or in various combinations, may help achieve these goals. Previous research has demonstrated a potential role for TLR9 agonists, such as CMP-001, in the treatment of patients with this disease. CMP-001 is an investigational agent composed of a virus-like particle, and may induce changes in the body's immune system that interfere with the melanoma cells' ability to grow or spread. Previous studies have shown CMP-001 to be well tolerated. The most common side effects are flu-like symptoms and hypotension, and these usually resolve in a few hours with supportive care.

The current standard of care for patients with operable melanoma is surgery, followed by adjuvant immunotherapy or targeted therapy. However, the EA6194 study is testing a neoadjuvant approach. Patients will receive either monotherapy with the PD-1 inhibitor pembrolizumab or pembrolizumab in combination with CMP-001. All patients will then proceed to surgery, followed by adjuvant treatment with pembrolizumab. EA6194 will determine both the effect of adding neoadjuvant immunotherapy alone, as well as the effect of adding neoadjuvant immunotherapy plus CMP-001.

EA6194's primary objective is to compare the pathologic complete response rate between arms. Secondary objectives include comparing the rate of pathologic near-complete/major response to the neoadjuvant therapy, recurrence-free survival, overall survival, the radiological/clinical preoperative response rate, safety, and toxicity between arms. The administration of CMP-001 will be via subcutaneous injection on day one, then intratumorally thereafter. The study will evaluate the pathologic response rate of injected versus un-injected lesions on the combination arm.

If successful, this trial may build the foundation for a definitive phase III trial in this population. The study will enable future biomarker and mechanistic studies.

Patients may be eligible for EA6194 if they have been diagnosed with melanoma, have not yet received any treatment, and are candidates for surgery.

This study is led by Ahmad Tarhini, MD, PhD (Moffitt Cancer Center) and Diwakar Davar, MD (University of Pittsburgh/Hillman Cancer Center).

Learn more about EA6194 at ecog-acrin.org.