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

Incyte Corporation308 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

308

Conditions

Squamous Cell Carcinoma of the Anal Canal

Interventions

carboplatinDRUG

carboplatin will be administered intravenous on Day 1 of each 28 day cycle

paclitaxelDRUG

paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle

retifanlimabDRUG

retifanlimab will be administered intravenous on Day 1 of each 28 day cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (84)

Outcomes

Primary Outcomes

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.

Time frame: up to 33.9 months

Secondary Outcomes

Overall Survival

Overall survival was defined as the time from the date of randomization until the date of death due to any cause.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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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

...and 74 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: up to 535 days

Number of Participants With Any TEAE During the Open-label Monotherapy Period

Time frame: up 457 days

Number of Participants With Any TEAE Leading to Discontinuation of Study Drug During the Open-label Monotherapy Period

Time frame: 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.

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

Cmin of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel

Cmin was defined as the minimum observed plasma concentration of retifanlimab.

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

Tmax of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel

tmax was defined as the time to the maximum serum concentration of retifanlimab.

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

AUC of Retifanlimab at Steady State When Administered With Carboplatin-paclitaxel

AUC was defined as the area under the serum concentration versus time curve.

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