TriangleNCT04472429 · CITED IN SOURCE DOCUMENTS
Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2026-09-02
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS)
Overall Survival
Objective Response Rate (ORR)
Duration of Response (DOR)
Disease Control Rate (DCR)
Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period
Number of Participants With Any TEAE During the Open-label Monotherapy Period
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period
Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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 1. * 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 Exclusion Criteria: * 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle
- intervention Names
- Drug: carboplatin
- Drug: paclitaxel
- label
- Group A : carboplatin+paclitaxel+placebo
- type
- PLACEBO_COMPARATOR
- description
- Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle
- intervention Names
- Drug: carboplatin
- Drug: paclitaxel
- Drug: retifanlimab
- label
- Group B : carboplatin+paclitaxel+retifanlimab
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Group A : carboplatin+paclitaxel+placebo
- Group B : carboplatin+paclitaxel+retifanlimab
- description
- carboplatin will be administered intravenous on Day 1 of each 28 day cycle
- name
- carboplatin
- type
- DRUG
- arm Group Labels
- Group A : carboplatin+paclitaxel+placebo
- Group B : carboplatin+paclitaxel+retifanlimab
- description
- paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle
- name
- paclitaxel
- type
- DRUG
- arm Group Labels
- Group B : carboplatin+paclitaxel+retifanlimab
- description
- retifanlimab will be administered intravenous on Day 1 of each 28 day cycle
- name
- retifanlimab
- other Names
- INCMGA00012
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- QUADRUPLE
- masking Description
- Double Blind
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 308
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Progression-free Survival (PFS)
- time Frame
- up to 33.9 months
- secondary Outcomes
- description
- Overall survival was defined as the time from the date of randomization until the date of death due to any cause.
- measure
- Overall Survival
- time Frame
- up to 56.5 months
- description
- ORR was defined as the percentage of participants with a confirmed 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.
- measure
- Objective Response Rate (ORR)
- time Frame
- up to 445 days
- description
- DOR was defined as the time from the first documented confirmed 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.
- measure
- Duration of Response (DOR)
- time Frame
- up to 32.1 months
- description
- 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.
- measure
- Disease Control Rate (DCR)
- time Frame
- up to 445 days
- description
- 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.
- measure
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period
- time Frame
- up to 535 days
- description
- 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.
- measure
- Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period
- time Frame
- up to 535 days
- description
- 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. AEs that occurred after new anticancer therapy were be excluded.
- measure
- Number of Participants With Any TEAE During the Open-label Monotherapy Period
- time Frame
- up 463 days
- description
- 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. AEs that occurred after new anticancer therapy were be excluded.
- measure
- Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period
- time Frame
- up 463 days
- description
- Cmax was defined as the maximum observed plasma concentration of retifanlimab.
- measure
- Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
- time Frame
- preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
- description
- Cmin was defined as the minimum observed plasma concentration of retifanlimab.
- measure
- Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
- time Frame
- preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
- description
- tmax was defined as the time to the maximum serum concentration of retifanlimab.
- measure
- Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
- time Frame
- preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
- description
- AUC was defined as the area under the serum concentration versus time curve.
- measure
- AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel
- time Frame
- preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4
Full study description
- 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.
Source references
- references
- citation
- Rao S, Samalin-Scalzi E, Evesque L, Ben Abdelghani M, Morano F, Roy A, Dahan L, Tamberi S, Dhadda AS, Saunders MP, Casanova N, Guimbaud R, Lievre A, Maurel J, Fakih M, Tian C, Harrison J, Jones MM, Cornfeld M, Spano JP, Rochefort P; POD1UM-303/InterAACT-2 study investigators. Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial. Lancet. 2025 Jun 14;405(10495):2144-2152. doi: 10.1016/S0140-6736(25)00631-2.
- pmid
- 40517007
- type
- DERIVED
- citation
- Rao S, Jones M, Bowman J, Tian C, Spano JP. POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022 Aug 24;12:935383. doi: 10.3389/fonc.2022.935383. eCollection 2022.
- pmid
- 36091159
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice