A Phase 2 Study to Investigate the Activity of Neoadjuvant PRTX007 Combined With Pembrolizumab in Participants With Stage III Melanoma (INFLECTION-003)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 11
- 主要终点
- Major Pathologic Response (MPR) Rate
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Neoadjuvant PRTX007 + Pembrolizumab (Response-Adapted Adjuvant Therapy)
Participants with resectable Stage III melanoma will receive neoadjuvant treatment with PRTX007 in combination with pembrolizumab prior to definitive surgical resection. Following surgery, participants will receive response-adapted adjuvant therapy based on pathologic response. Participants achieving a major pathologic response (MPR) may receive observation or pembrolizumab alone, while participants without MPR will receive adjuvant PRTX007 in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
Neoadjuvant PRTX007 + Pembrolizumab (Response-Adapted Adjuvant Therapy)
Participants with resectable Stage III melanoma will receive neoadjuvant treatment with PRTX007 in combination with pembrolizumab prior to definitive surgical resection. Following surgery, participants will receive response-adapted adjuvant therapy based on pathologic response. Participants achieving a major pathologic response (MPR) may receive observation or pembrolizumab alone, while participants without MPR will receive adjuvant PRTX007 in combination with pembrolizumab.
干预措施: PRTX007 (Drug)
结局指标
主要结局
Major Pathologic Response (MPR) Rate
时间窗: 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.
次要结局
- Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-Related AEs (irAEs), and Dose-Limiting Toxicities (DLTs)(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(Baseline through end of study (approximately up to 52 weeks))
- Pathologic Complete Response (pCR) Rate(At time of surgical resection (approximately 9 weeks after initiation of treatment))
- Event-Free Survival (EFS)(From first dose up to 1 year)
- Overall Survival (OS)(From first dose through end of study (approximately up to 52 weeks or longer if followed))
- Pharmacokinetics of PRTX007(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(Baseline through treatment period (up to approximately 9 weeks and selected later time points))
- Changes in mRNA expression(Baseline through treatment period (up to approximately 9 weeks and selected later time points))
- Changes in immune cell activation and proliferation markers(Baseline through treatment period (up to approximately 9 weeks and selected later time points))