Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).
- Conditions
- Squamous Cell Carcinoma of the Anal Canal
- Interventions
- Registration Number
- NCT04472429
- Lead Sponsor
- Incyte Corporation
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 308
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Able to comprehend and willing to sign a written ICF for the study.
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Are 18 years of age or older (or as applicable per local country requirements).
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Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC.
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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.
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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.
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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.
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ECOG performance status 0 to 1.
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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.
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Willingness to avoid pregnancy or fathering children
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- 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 1.
- 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 v5.
- Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B : carboplatin+paclitaxel+retifanlimab carboplatin Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle Group B : carboplatin+paclitaxel+retifanlimab paclitaxel Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle Group B : carboplatin+paclitaxel+retifanlimab retifanlimab Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle Group A : carboplatin+paclitaxel+placebo paclitaxel Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle Group A : carboplatin+paclitaxel+placebo carboplatin Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) 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.
- Secondary Outcome Measures
Name Time Method Overall Survival up to 40.4 months Overall survival was defined as the time from the date of randomization until the date of death due to any cause.
Objective Response Rate (ORR) up to 445 days ORR was defined as the percentage of participants with a CR or PR at any post-Baseline visit before the first PD or new anticancer therapy, according to RECIST v1.1 as determined by BICR. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
Duration of Response (DOR) up to 32.1 months DOR was defined as the time from the first documented response (CR or PR) determined by BICR to the time of first documented disease progression per RECIST v1.1 or death due to any cause. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.
Disease Control Rate (DCR) up to 445 days DCR was defined as the percentage of participants maintaining either a confirmed overall response of CR or PR or stable disease (SD) at any post-Baseline visit before the first PD or new anticancer therapy, according to RECIST v1.1 as determined by BICR. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period up to 535 days An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of a pre-existing events after the first dose of study treatment and within 90 days of the last administration of retifanlimab/placebo, or within 30 days of the last chemotherapy. AEs that occurred after new anticancer therapy were be excluded.
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period up to 535 days An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of a pre-existing events after the first dose of study treatment and within 90 days of the last administration of retifanlimab/placebo, or within 30 days of the last chemotherapy. AEs that occurred after new anticancer therapy were be excluded.
Number of Participants With Any TEAE During the Open-label Monotherapy Period up 457 days An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of a pre-existing events after the first dose of study treatment and within 90 days of the last administration of retifanlimab/placebo, or within 30 days of the last chemotherapy. AEs that occurred after new anticancer therapy were be excluded.
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period up 457 days An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of a pre-existing events after the first dose of study treatment and within 90 days of the last administration of retifanlimab/placebo, or within 30 days of the last chemotherapy. AEs that occurred after new anticancer therapy were be excluded.
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 Cmax was defined as the maximum observed plasma concentration of retifanlimab.
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 Cmin was defined as the minimum observed plasma concentration of retifanlimab.
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 tmax was defined as the time to the maximum serum concentration of retifanlimab.
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 AUC was defined as the area under the serum concentration versus time curve.
Trial Locations
- Locations (83)
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Ochsner Clinic
🇺🇸New Orleans, Louisiana, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Texas Oncology
🇺🇸Austin, Texas, United States
Baylor Scott and White Research Institute
🇺🇸Dallas, Texas, United States
Scroll for more (73 remaining)The University of Arizona Cancer Center🇺🇸Tucson, Arizona, United States