Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).

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)

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Anal Canal
• Intervention / Treatment: Drug: carboplatin; Drug: paclitaxel; Drug: retifanlimab

• Study Type: Interventional
• Enrollment (Actual): 308
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 04102
      • Princess Alexandra Hospital Australia
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia, 03168
      • Monash Medical Centre Clayton
• Belgium
  • Antwerp, Belgium, 02020
    • ZNA Middelheim
  • Brussels, Belgium, 01070
    • Ulb Hospital Erasme
• Denmark
  • Herlev, Denmark, 02730
    • Herlev og Gentofte Hospital
  • Vejle, Denmark, 07100
    • Vejle Hospital
• France
  • Angers, France, 49055
    • Institut de Cancerologie de L Ouest - Site Paul Papin
  • Besançon, France, 25030
    • Chu Besancon Hospital Jean Minjoz
  • Bordeaux, France, 33075
    • Centre Hospitalier Universitaire de Bordeaux
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Marseille, France, 13385
    • CHU Hôpital de la Timone
  • Montpellier, France, 34298
    • Institut du Cancer de Montpellier
  • Nice, France, 06200
    • Centre Antoine Laccassagne
  • Paris, France, 75651
    • Hospital Universitaire Pitie-Salpetriere
  • Poitiers, France, 86021
    • Hospital de La Miletrie
  • Rennes, France, 35033
    • Chu de Rennes - Hospital Pontchaillou
  • Rouen, France, 76031
    • Hopital Charles Nicolle Chu Rouen Hospital de Bois-Guillaume
  • Saint-Herblain, France, 44800
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Strasbourg, France, 67200
    • Institut de Cancerologie de Strasbourg
  • Toulouse, France, 31059
    • Chu Toulouse Hopital Rangueil
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Bonn, Germany, 53127
    • Universitatsklinikum Bonn Aoer
  • Dresden, Germany, 01307
    • University Clinic Carl Gustav Carus Technical University Dresden
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
• Italy
  • Milan, Italy, 20141
    • European Institute of Oncology
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Milan, Italy, 20133
    • Comitato Etico Fondazione Irccs Istituto Nazionale Dei Tumori Milano
  • Monserrato, Italy, 09042
    • University Di Cagliari-Presidio Policlinico Monserrato
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria University Degli Studi Della Campania Luigi Vanvitelli
  • Padua, Italy, 35128
    • Iov - Istituto Oncologico Veneto Irccs
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Rimini, Italy, 47923
    • Ospedale degli Infermi
  • San Giovanni Rotondo, Italy, 71013
    • I.R.C.C.S. Casa Sollievo Della Sofferenza
  • Torrette, Italy, 60020
    • Azienda Ospedaliero Universitaria Ospedali Riuniti
• Japan
  • Chūōku, Japan, 104-0045
    • National Cancer Center Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hidaka-shi, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Nagoya, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Shinjuku-ku, Japan, 162-8655
    • Center Hospital of the National Center for Global Health and Medicine
• Norway
  • Bergen, Norway, 05021
    • Haukeland University Hospital
  • Oslo, Norway, 00450
    • Oslo Universitetssykehus
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Panoncology Trials Pan American Center For Oncology Trials, Llc
• Spain
  • A Coruña, Spain, 15006
    • Complejo Hospitalario Universitario A Coruña
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Palma de Mallorca, Spain, 07120
    • Son Espases University Hospital
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sahlgrenska University Hospital
  • Lund, Sweden, 22185
    • Skaenes Universitetssjukhus Lund
  • Stockholm, Sweden, 118 83
    • Stockholm South General Hospital Sodersjukhuset
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital
  • Hull, United Kingdom, HU16 5JQ
    • Castle Hill Hospital
  • Leeds, United Kingdom, LS 9 7TF
    • Leeds Teaching Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Nhs Foundation Trust - Chelsea
  • Manchester, United Kingdom, M20 4BV
    • The Christie Nhs Foundation Trust Uk
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Nhs Foundation Trust - Sutton
  • Truro, United Kingdom, TR1 3LQ
    • Royal Cornwall Hospital Truro Sunrise Centre
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Maryland Oncology Hematology, P.A.
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Baylor Scott and White Research Institute
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical Consultants Llc
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology-Wichita Falls Texoma Cancer Center
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Virginia Cancer Specialists, PC
    • Roanoke, Virginia, United States, 24014
      • Blue Ridge Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group A : carboplatin+paclitaxel+placebo; Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle	Drug: carboplatin; carboplatin will be administered intravenous on Day 1 of each 28 day cycle; Drug: paclitaxel; paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle
Experimental: Group B : carboplatin+paclitaxel+retifanlimab; Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle	Drug: carboplatin; carboplatin will be administered intravenous on Day 1 of each 28 day cycle; Drug: paclitaxel; paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle; Drug: retifanlimab; retifanlimab will be administered intravenous on Day 1 of each 28 day cycle; Other Names: INCMGA00012

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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.	up to 33.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as the time from the date of randomization until the date of death due to any cause.	up to 40.4 months
Objective Response Rate (ORR)	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.	up to 445 days
Duration of Response (DOR)	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.	up to 32.1 months
Disease Control Rate (DCR)	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.	up to 445 days
Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period	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.	up to 535 days
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period	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.	up to 535 days
Number of Participants With Any TEAE During the Open-label Monotherapy Period	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.	up 457 days
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period	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.	up 457 days
Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel	Cmax was defined as the maximum observed plasma concentration of retifanlimab.	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	Cmin was defined as the minimum observed plasma concentration of retifanlimab.	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	tmax was defined as the time to the maximum serum concentration of retifanlimab.	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 of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel	AUC was defined as the area under the serum concentration versus time curve.	preinfusion on Day 1 of Cycles 1, 2, 4, 6, 8, and 12; immediately after infusion on Day 1 of Cycles 1 and 4

Collaborators and Investigators

• Sponsor: Incyte Corporation

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): April 15, 2024
• Study Completion (Actual): September 26, 2025

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (Actual): July 15, 2020

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: paclitaxel; carboplatin; Squamous cell carcinoma; Anal Cancer; PD-1 Inhibitor; SCAC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Squamous Cell; Anus Diseases; Rectal Neoplasms; Carcinoma, Squamous Cell; Anus Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel
• Other Study ID Numbers: INCMGA 0012-303; 2020-000826-24 (EudraCT Number); 2024-512331-72-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No