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

A Phase 2 Study to Investigate the Activity of Neoadjuvant PRTX007 Combined With Pembrolizumab in Participants With Stage III Melanoma (INFLECTION-003)

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

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