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NCT Number: NCT07565285

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

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.

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Key information

Conditions

Melanoma Stage III Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Calvary Mater Newcastle, Waratah, New South Wales, Australia

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PRTX007

Drug

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)

Pembrolizumab

Drug

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

Primary outcomes

  1. Major Pathologic Response (MPR) Rate

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

    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.

Secondary outcomes

  1. Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-Related AEs (irAEs), and Dose-Limiting Toxicities (DLTs)

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

    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.

  2. 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)

  3. Pathologic Complete Response (pCR) Rate

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

    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.

  4. Event-Free Survival (EFS)

    Time frame: From first dose up to 1 year

    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.

  5. Overall Survival (OS)

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

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

  6. Pharmacokinetics of PRTX007

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

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

  7. 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)

  8. Changes in mRNA expression

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

  9. Changes in immune cell activation and proliferation markers

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

Study contacts

Contact information is provided by the study sponsor or research team.

Gunjan Mody

CONTACT

[email protected]

+61 2 9199 9596

Sponsors and collaborators

Lead sponsor

Primmune Therapeutics, Inc.

Industry

Registry information

Official study title

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

Acronym: INFLECTION-003

Important dates

Study start
2026
Primary completion
2027
Study completion
2029
First posted
May 4, 2026
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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