The Efficacy and Safety of PRTX007-003 Combined With Pembrolizumab in Resectable Stage III Melanoma

Phase 2RecruitingNCT07565285

Primmune Therapeutics, Inc.48 enrolled

Overview

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.

This study investigates whether combining the TLR7 agonist PRTX007 with pembrolizumab enhances immune-mediated tumor response in the neoadjuvant setting for Stage III melanoma, with the goal of improving pathologic response rates and clinical outcomes while maintaining an acceptable safety profile. Design This is a Phase 2, multi-center, open-label, single-arm study conducted in Australia. The study will enroll approximately 48 participants with resectable Stage III melanoma. The study consists of two parts: * Part A: 24 participants will be enrolled, including an initial dose-escalation safety run-in using a 3+3 design to evaluate tolerability and dose-limiting toxicities. * Part B: An additional 24 participants will be enrolled if sufficient activity is observed in Part A. Treatment Plan Participants will receive neoadjuvant therapy consisting of: * PRTX007: Oral administration for 3 days on and 4 days off per week for 9 cycles (7-day cycles) * Pembrolizumab: 200 mg intravenous infusion every 3 weeks for 3 cycles Following completion of neoadjuvant therapy, participants will undergo definitive surgical resection. Post-surgical treatment will be response-adapted: * Participants achieving MPR may receive observation or pembrolizumab alone * Participants without MPR will receive adjuvant PRTX007 in combination with pembrolizumab

Study Type

INTERVENTIONAL

Allocation

Interventions

PRTX007DRUG

PRTX007 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)

PembrolizumabDRUG

Pembrolizumab 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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 * Adequate organ function * Able to provide written informed consent Exclusion Criteria: * 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 * Women who are pregnant or breastfeeding * Recent treatment with another investigational therapy * Any condition that, in the opinion of the investigator, would interfere with study participation or safety

Locations (7)

Calvary Mater Newcastle

Waratah, New South Wales, Australia

RECRUITING

Cairns And Hinterland Hospital And Health Service

Cairns, Queensland, Australia

NOT_YET_RECRUITING

Gallipoli Medical Research

Greenslopes, Queensland, Australia

NOT_YET_RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

NOT_YET_RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

NOT_YET_RECRUITING

One Clinical Research Pty Ltd

Nedlands, Western Australia, Australia

RECRUITING

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: At time of surgical resection (approximately 9 weeks after initiation of treatment)

Secondary Outcomes

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.

Time frame: From first dose of study treatment through end of study (approximately up to 52 weeks)

Number of participants with abnormal physical examination findings, abnormal vital signs, abnormal Eastern Cooperative Oncology Group (ECOG) performance status, and abnormal clinical laboratory parameters

Time frame: Baseline through end of study (approximately up to 52 weeks)

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.

Time frame: At time of surgical resection (approximately 9 weeks after initiation of treatment)

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.

Time frame: From first dose up to 1 year

Overall Survival (OS)

Overall survival is defined as the time from first dose of study treatment to death from any cause.

Time frame: From first dose through end of study (approximately up to 52 weeks or longer if followed)

Pharmacokinetics of PRTX007

Plasma concentrations of PRTX007 and its active metabolite will be measured to characterize pharmacokinetic parameters using validated analytical methods.

Time frame: During treatment period (multiple time points from baseline through approximately 9 weeks and selected later time points)

Changes in cytokine, chemokine and soluble PD-1/PD-L1 biomarkers

Time frame: Baseline through treatment period (up to approximately 9 weeks and selected later time points)

Changes in mRNA expression

Time frame: Baseline through treatment period (up to approximately 9 weeks and selected later time points)

Changes in immune cell activation and proliferation markers

Time frame: Baseline through treatment period (up to approximately 9 weeks and selected later time points)

The Efficacy and Safety of PRTX007-003 Combined With Pembrolizumab in Resectable Stage III Melanoma

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts