This Phase 2, multi-center, single-arm study evaluates the safety, tolerability, and activity of neoadjuvant PRTX007 in combination with pembrolizumab in participants with resectable Stage III melanoma. Neoadjuvant immunotherapy has demonstrated improved clinical outcomes compared with adjuvant-only approaches, but there remains a need to enhance pathologic response rates without significant added toxicity.
Participants will receive oral PRTX007, a Toll-like receptor 7 (TLR7) agonist prodrug, administered in combination with intravenous pembrolizumab prior to surgical resection. The primary objective is to determine the major pathologic response (MPR) rate following neoadjuvant therapy. Secondary objectives include evaluation of safety, pathologic complete response, event-free survival, overall survival, pharmacokinetics, and immune-related biomarkers.
This study aims to determine whether the addition of PRTX007 to pembrolizumab improves antitumor immune responses and clinical outcomes in patients with Stage III melanoma.
Adults aged 18 years or older
Histologically confirmed, resectable Stage III cutaneous melanoma.
Candidate for curative-intent surgical resection
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Prior systemic therapy for melanoma, including immunotherapy
Uveal melanoma or mucosal melanoma.
Active autoimmune disease requiring systemic treatment
Primary immunodeficiency or use of systemic immunosuppressive therapy
Single group
PRTX007
DrugPRTX007 is an orally administered prodrug of PRX034, a Toll-like receptor 7 (TLR7) agonist designed to activate innate and adaptive immune responses. NEOADJUVANT REGIMEN * 600 mg orally once daily (safety run-in participants) or * 750 mg orally once daily (subsequent participants) * Administered 3 days on, 4 days off (7-day cycle) * Total of 9 cycles (9 weeks) ADJUVANT REGIMEN (IF NO MPR) * 750 mg orally once daily * Administered 3 days on, 4 days off * Total of 12 cycles (12 weeks)
Pembrolizumab
DrugPembrolizumab is a programmed cell death protein-1 (PD-1) blocking antibody administered by intravenous infusion NEOADJUVANT REGIMEN * 200 mg IV every 3 weeks (Q3W) * Total of 3 cycles (9 weeks) ADJUVANT REGIMEN * 400 mg IV every 6 weeks (Q6W) for 7 cycles OR * 200 mg IV every 3 weeks (Q3W) for 14 cycles * Total duration: approximately 42 weeks
Major Pathologic Response (MPR) Rate
Major pathologic response (MPR) is defined as ≤10% residual viable tumor cells in the resected tumor specimen following completion of neoadjuvant therapy, as assessed by central pathology review.
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-Related AEs (irAEs), and Dose-Limiting Toxicities (DLTs)
Number and severity of adverse events, serious adverse events, immune-related adverse events, and dose-limiting toxicities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0.
Number of participants with abnormal physical examination findings, abnormal vital signs, abnormal Eastern Cooperative Oncology Group (ECOG) performance status, and abnormal clinical laboratory parameters
Pathologic Complete Response (pCR) Rate
Pathologic complete response (pCR) is defined as the absence of residual viable tumor cells (0%) in the resected tumor specimen following neoadjuvant therapy, as assessed by central pathology review.
Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the time from first dose of study treatment to any of the following events: disease progression or toxicity preventing surgery during neoadjuvant treatment; recurrence of disease after surgery; failure to achieve complete resection (R0 or R1); or death from any cause.
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