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NCT04472429

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

Completed Phase 3 Results posted Last updated 3 November 2025
What this trial tests

Phase 3 trial testing carboplatin in Squamous Cell Carcinoma of the Anal Canal in 308 participants. Completed in 26 September 2025.

Timeline
12 January 2021
Primary endpoint
15 April 2024
26 September 2025

Quick facts

Lead sponsorIncyte Corporation
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment308
Start date12 January 2021
Primary completion15 April 2024
Estimated completion26 September 2025
Sites84 locations across Denmark, France, Italy, Japan, Belgium, Sweden, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Incyte Corporation — full company profile →

Who can join

18 and older, any sex, with Squamous Cell Carcinoma of the Anal Canal. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) Primary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy9.37.5 – 11.3
Placebo + Chemotherapy7.47.1 – 7.7
Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) During the Randomized Period Secondary · 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 la

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy154
Placebo + Chemotherapy152
Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Randomized Period Secondary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy17
Placebo + Chemotherapy4
Cmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel Secondary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy209± 27.9
Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel Secondary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy49.5± 59.4
Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel Secondary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy0.720± 35.8
AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel Secondary · 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.

GroupValue95% CI
Retifanlimab 500 mg Q4W + Chemotherapy2490± 40.1

Adverse events — posted to ClinicalTrials.gov

Time frame: up to approximately 33 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo + Chemotherapy
Serious: 59/152 (39%)
Deaths: 38/152
Retifanlimab 500 mg Q4W + Chemotherapy
Serious: 73/154 (47%)
Deaths: 53/154
Randomized Period Total
Serious: 132/306 (43%)
Deaths: 91/306
Retifanlimab 500 mg Q4W
Serious: 16/69 (23%)
Deaths: 35/69

Serious adverse events (141 terms)

ReactionSystemPlacebo + ChemotherapyRetifanlimab 500 mg Q4W + …Randomized Period TotalRetifanlimab 500 mg Q4W
SepsisInfections and infestations
DiarrhoeaGastrointestinal disorders
Urinary tract infectionInfections and infestations
VomitingGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Acute kidney injuryRenal and urinary disorders
Febrile neutropeniaBlood and lymphatic system disorders
Neutropenic sepsisInfections and infestations
Anal abscessInfections and infestations
Female genital tract fistulaReproductive system and breast disorders
HydronephrosisRenal and urinary disorders
NauseaGastrointestinal disorders
PyelonephritisInfections and infestations
Abdominal painGastrointestinal disorders
Adrenal insufficiencyEndocrine disorders
Anal fistulaGastrointestinal disorders
AstheniaGeneral disorders
Blood bilirubin increasedInvestigations
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Confusional statePsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Other adverse events (65 terms — click to expand)

ReactionSystemPlacebo + ChemotherapyRetifanlimab 500 mg Q4W + …Randomized Period TotalRetifanlimab 500 mg Q4W
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
ConstipationGastrointestinal disorders
FatigueGeneral disorders
Neuropathy peripheralNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
White blood cell count decreasedInvestigations
ParaesthesiaNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
COVID-19Infections and infestations
PyrexiaGeneral disorders
LeukopeniaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Platelet count decreasedInvestigations
Urinary tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
ProctalgiaGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
Abdominal pain upperGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Rectal haemorrhageGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
HypothyroidismEndocrine disorders
LymphopeniaBlood and lymphatic system disorders
Mucosal inflammationGeneral disorders

Most-reported serious reactions: Sepsis, Diarrhoea, Urinary tract infection, Vomiting, Pulmonary embolism, Pyrexia, Anaemia, Pneumonia.

Data from ClinicalTrials.gov NCT04472429 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  2. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  3. Antibodies to watch in 2023.
    Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
  4. Anal Cancer: The Past, Present and Future.
    Gondal TA, Chaudhary N, Bajwa H, Rauf A, et al · · 2023 · cited 57× · PMID 36975459 · DOI 10.3390/curroncol30030246
  5. A phase II study of retifanlimab (INCMGA00012) in patients with squamous carcinoma of the anal canal who have progressed following platinum-based chemotherapy (POD1UM-202).
    Rao S, Anandappa G, Capdevila J, Dahan L, et al · · 2022 · cited 53× · PMID 35816951 · DOI 10.1016/j.esmoop.2022.100529
  6. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study.
    Marabelle A, Cassier PA, Fakih M, Kao S, et al · · 2022 · cited 53× · PMID 35114169 · DOI 10.1016/s2468-1253(21)00382-4
  7. Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: the CARACAS study.
    Lonardi S, Prete AA, Morano F, Messina M, et al · · 2021 · cited 35× · PMID 34815354 · DOI 10.1136/jitc-2021-002996
  8. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of gastrointestinal cancer.
    Kelly RJ, Bever K, Chao J, Ciombor KK, et al · · 2023 · cited 20× · PMID 37286304 · DOI 10.1136/jitc-2022-006658

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