NCT04472429已完成3 期
A Phase 3 Global, Multicenter, Double-Blind Randomized Study of Carboplatin-Paclitaxel With INCMGA00012 or Placebo in Participants With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal Not Previously Treated With Systemic Chemotherapy (POD1UM-303/InterAACT 2)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 308
- 试验地点
- 166
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This study is a Phase 3 global, multicenter, placebo-controlled double-blind randomized study that will enroll participants with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double Blind
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
- •Able to comprehend and willing to sign a written ICF for the study.
- •Are 18 years of age or older (or as applicable per local country requirements).
- •Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC.
- •No prior systemic therapy other than the following: a. Chemotherapy administered concomitantly with radiotherapy as a radiosensitizing agent is permitted.
- •b. Prior neoadjuvant or adjuvant therapy if completed ≥ 6 months before study entry.
- •Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
- •Able and willing to provide adequate tissue sample and whole blood sample with central testing result prior to randomization. Biopsy for archival samples should have occurred within 9 months prior to randomization.
- •ECOG performance status 0 to
- •If HIV-positive, then must be stable as defined by: a. CD4+ count ≥ 200/μL, b. Undetectable viral load per standard of care assay, c. Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and have not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment.
- •Willingness to avoid pregnancy or fathering children
排除标准
- •Has received prior PD-(L)1 directed therapy
- •Has received prior radiotherapy with or without radiosensitizing chemotherapy within 28 days of Cycle 1 Day 1 except for palliative radiation (30 Gy or less) which is restricted for 14 days of Cycle 1 Day 1 (note: all toxicities associated should have resolved to Grade ≤ 1).
- •Participants with laboratory outside of the protocol defined ranges.
- •History of second malignancy within 3 years (with exceptions).
- •Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders.
- •Active bacterial, fungal, or viral infections, including hepatitis A, B, and C and IV antibiotic use within 7 days of Cycle 1 Day
- •Receipt of a live vaccine within 28 days of planned start of study therapy.
- •History of organ transplant, including allogeneic stem cell transplantation.
- •Known active CNS metastases and/or carcinomatous meningitis.
- •Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids).
- •Participant is pregnant or breastfeeding.
- •Current use of protocol defined prohibited medication.
- •Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v
- •Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements
研究组 & 干预措施
Group A : carboplatin+paclitaxel+placebo
Placebo Comparator
Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle
干预措施: carboplatin (Drug)
Group A : carboplatin+paclitaxel+placebo
Placebo Comparator
Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle
干预措施: paclitaxel (Drug)
Group B : carboplatin+paclitaxel+retifanlimab
Experimental
Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle
干预措施: paclitaxel (Drug)
Group B : carboplatin+paclitaxel+retifanlimab
Experimental
Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle
干预措施: carboplatin (Drug)
Group B : carboplatin+paclitaxel+retifanlimab
Experimental
Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle
干预措施: retifanlimab (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: up to 33.9 months
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review committee (BICR), or death due to any cause, whichever occurred first. PD: progression of a target or non-target lesion or presence of a new lesion.
次要结局
- AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel(preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4)
- Overall Survival(up to 40.4 months)
- Disease Control Rate (DCR)(up to 445 days)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period(up to 535 days)
- Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period(up to 535 days)
- Number of Participants With Any TEAE During the Open-label Monotherapy Period(up 457 days)
- Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period(up 457 days)
- Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel(preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4)
- Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel(preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4)
- Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel(preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4)
- Objective Response Rate (ORR)(up to 445 days)
- Duration of Response (DOR)(up to 32.1 months)
- Overall Survival(up to 56.5 months)
- Number of Participants With Any TEAE During the Open-label Monotherapy Period(up 463 days)
- Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period(up 463 days)
研究者
研究点 (166)
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相关资讯
Japan Approves Zynyz for First-Line Treatment of Advanced Anal Cancer- Japan's Ministry of Health, Labour and Welfare approved Zynyz (retifanlimab) in combination with carboplatin and paclitaxel as the first and only first-line treatment for advanced squamous cell carcinoma of the anal canal.
- The approval was based on Phase 3 POD1UM-303/InterAACT2 trial data showing a statistically significant 37% reduction in risk of progression or death compared to placebo combination.
- Patients receiving Zynyz combination therapy achieved a median progression-free survival of 9.3 months versus 7.4 months for placebo combination group.
- This marks the first regulatory approval for Zynyz in Japan and the second global approval for this indication following FDA approval in May 2025.9 months agoRetifanlimab Plus Chemotherapy Shows Promise in Advanced Squamous Cell Anal Carcinoma- Phase 3 POD1UM-303 trial shows retifanlimab combined with chemotherapy significantly improves progression-free survival in patients with locally recurrent or metastatic squamous cell anal carcinoma (SCAC).
- The combination therapy demonstrated a median PFS of 9.3 months compared to 7.4 months with chemotherapy alone, marking a potential new standard of care.
- Interim overall survival data also suggest a trend towards improvement with the addition of retifanlimab, with manageable immune-related adverse effects.
- The study's success supports a planned supplemental biologics license application (sBLA) for retifanlimab, offering hope for addressing unmet needs in SCAC treatment.last yearZynyz Plus Chemotherapy Shows Promise in Advanced Anal Cancer- Incyte's Zynyz (retifanlimab) combined with chemotherapy significantly improved progression-free survival in previously untreated patients with advanced anal cancer.
- The Phase III POD1UM-303 trial is the first and largest study evaluating a first-line checkpoint inhibitor for advanced anal cancer, addressing a high unmet medical need.
- Zynyz plus platinum-based chemotherapy may represent a new standard of care for patients with advanced squamous cell anal cancer, according to study presenter Sheela Rao.
- Incyte plans to seek FDA approval for Zynyz in anal cancer based on these findings, potentially offering a new treatment option.2 years agoRetifanlimab Plus Chemotherapy Improves PFS in Advanced Anal Cancer- The POD1UM-303 trial demonstrated that adding retifanlimab to carboplatin and paclitaxel significantly improved progression-free survival (PFS) in patients with recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).
- Patients receiving retifanlimab plus chemotherapy experienced a median PFS of 9.3 months compared to 7.4 months with placebo plus chemotherapy, showing a statistically significant improvement.
- The combination therapy also led to a higher overall response rate (ORR) and a longer duration of response (DOR) compared to placebo plus chemotherapy in this patient population.
- Interim overall survival (OS) data suggest a trend towards improved survival with retifanlimab, indicating a potential new standard of care for advanced SCAC.2 years agoRetifanlimab Plus Chemotherapy Improves Outcomes in Advanced Anal Cancer- The POD1UM-303 trial showed that adding retifanlimab to carboplatin and paclitaxel significantly improved progression-free survival in patients with recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC).
- Patients receiving retifanlimab plus chemotherapy had a median PFS of 9.3 months compared to 7.4 months with chemotherapy alone (HR, 0.63; P = .0006).
- The combination therapy also demonstrated a higher overall response rate (56% vs 44%) and a longer duration of response (14.0 months vs 7.2 months).
- Interim overall survival data favored the retifanlimab arm, suggesting a potential new standard of care for advanced SCAC.2 years ago
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