Phase 3 Randomized Study of Carboplatin-Paclitaxel with Retifanlimab vs. Placebo in Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal
- Trial ID
- 2024-512331-72-00
- Sponsor
- Incyte Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of the combination of carboplatin-paclitaxel with INCMGA00012 compared to carboplatin-paclitaxel with placebo in participants with inoperable locally advanced or metastatic **Squamous Cell Carcinoma of the Anal Canal** (SCAC) who have not previously received systemic chemotherapy. This is clinically relevant as it aims to determine the potential benefit of adding INCMGA00012 to the standard chemotherapy regimen, which could lead to improved treatment outcomes for this patient population.
Secondary objectives include comparing the overall survival (OS) of the two treatment regimens in the same patient population. This comparison is crucial for understanding the long-term benefits and potential survival advantage offered by the addition of INCMGA00012 to the standard treatment protocol.
Participants
The clinical trial involves a total of **107 participants** diagnosed with **Squamous Carcinoma of the Anal Canal**. The study population includes both male and female subjects, aged **18 years and older**, who have inoperable locally advanced or metastatic conditions and have not previously received systemic chemotherapy. Participants were selected based on their ability to comprehend and sign an informed consent form, and they must have a measurable disease as per RECIST v1.1 criteria. The trial includes individuals with an **ECOG performance status** of 0 to 1, ensuring they are in relatively stable health. Participants with HIV are included if they meet specific stability criteria, such as a CD4+ count of at least 200/μL and an undetectable viral load. The trial population is characterized by a willingness to adhere to pregnancy prevention measures throughout the study duration. The selection process also considers the ability to provide adequate tissue and blood samples for central testing. The trial does not exclude vulnerable populations, indicating a comprehensive approach to participant inclusion.
Plans and Procedures
The clinical trial is a **Phase 3**, global, multicenter, double-blind, randomized study designed to evaluate the efficacy of **carboplatin-paclitaxel** combined with **retifanlimab** versus carboplatin-paclitaxel with placebo in participants with inoperable locally recurrent or metastatic **squamous cell carcinoma of the anal canal** (SCAC) who have not previously received systemic chemotherapy. The trial aims to assess progression-free survival (PFS) as the primary endpoint, with secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and the incidence of adverse events (AEs).
The trial is structured to include an initial screening visit to determine participant eligibility based on specific inclusion criteria, such as age, disease status, and prior treatment history. Participants must provide informed consent and meet criteria such as having measurable disease per RECIST v1.1 and an ECOG performance status of 0 to 1. The trial will involve multiple study visits, including regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. The estimated duration of the trial is from January 19, 2021, to February 24, 2025, with participant involvement expected to last up to 13 cycles of treatment, depending on individual response and tolerance.
Participants will be randomly assigned to receive either the investigational drug retifanlimab or a placebo, in combination with carboplatin and paclitaxel, administered via intravenous infusion. The study is double-blind, meaning neither the participants nor the investigators will know which treatment the participants are receiving, to ensure unbiased results. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent by the participant. The trial is not classified as low intervention, given the investigational nature of the drug in the population involved.
Treatment
The clinical trial involves the administration of **Retifanlimab (INCMGA00012)**, a **solution for infusion** developed by Incyte Corporation. This experimental medication is administered intravenously at a maximum daily dose of 500 mg, with a total maximum dose of 13,000 mg over a treatment period of 13 weeks. Retifanlimab is a protein-based therapeutic agent, specifically designed for intravenous use, and is not formulated for pediatric patients. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
A **placebo liquid**, identical in appearance to the Retifanlimab solution but devoid of the active substance, is used as a comparator in the study. The placebo is administered in a similar manner to the experimental drug, ensuring blinding of the study participants and investigators. The placebo serves to evaluate the efficacy of Retifanlimab by providing a control for comparison.
In addition to the experimental treatment, the trial includes the administration of **Carboplatin**, marketed as CARBOPLATINE ACCORD 10 mg/ml, a **solution for infusion** produced by Accord Healthcare France SAS. Carboplatin is a chemical-based agent used in the treatment regimen, administered intravenously with a maximum daily dose of 750 mg and a total maximum dose of 4,500 mg over a 6-week period. This standard-of-care therapy is a critical component of the treatment protocol for participants with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal.
**Paclitaxel**, marketed as Bendatax 6 mg/ml, is another **solution for infusion** included in the trial, provided by Bendalis GmbH. This chemical-based agent is administered intravenously at a maximum daily dose of 80 mg/m², with a total maximum dose of 1,440 mg/m² over a 6-week period. Paclitaxel is used in combination with Carboplatin to form the standard chemotherapy regimen against which the efficacy of Retifanlimab is compared. The administration of both Carboplatin and Paclitaxel follows a strict dosing schedule, with participant compliance closely monitored to ensure the integrity of the trial results.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the time from the date of randomization until disease progression according to RECIST v1.1 by Blinded Independent Central Review (BICR) or death due to any cause. Secondary endpoints include **Overall Survival (OS)**, defined as the time from the date of randomization until death due to any cause, and **Objective Response Rate (ORR)**, which is the percentage of participants achieving a Complete Response (CR) or Partial Response (PR) as determined by BICR according to RECIST v1.1. Additionally, **Duration of Response (DOR)** is measured from the first documented response until disease progression or death, and **Disease Control Rate (DCR)** is defined as the number of participants maintaining either an ORR or stable disease. The trial will also monitor the number of participants experiencing adverse events (AEs) and those discontinuing the study drug due to AEs.
The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial. The assessments will be conducted using validated scales and methodologies, ensuring consistency and reliability in the measurement of outcomes. The trial is designed to compare the efficacy of carboplatin-paclitaxel with INCMGA00012 versus carboplatin-paclitaxel with placebo in participants with inoperable locally advanced or metastatic Squamous Cell Carcinoma of the Anal Canal (SCAC) not previously treated with systemic chemotherapy. The study is a Phase 3, global, multicenter, double-blind, randomized trial, with an estimated end date of February 24, 2025.
Inclusion and Exclusion 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, and after any tissue collected during biopsy. 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 based on the criteria below. a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 120 days after the last dose of INCMGA00012 or placebo or through 180 days after the last dose of chemotherapeutic agents, whichever occurs later (or longer as appropriate based on country-specific requirements) and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b. Women of childbearing potential must have a negative serum pregnancy test at screening, agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty), and refrain from donating oocytes from screening through 120 days after the last dose of INCMGA00012 or placebo or through 180 days after the last dose of chemotherapeutic agents, whichever occurs later. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. The definition of WOCBP is located in Appendix A. c. Women of nonchildbearing potential (ie, per Appendix A) are eligible.
- See Appendix D for vaccination-related information.
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 (or 14 days for palliative radiotherapy (30Gy or less) that is not directed to the pelvic region. (Note: all toxicities associated should have resolved to Grade ≤ 1).
- Participants with laboratory values at screening defined in Table 8 of the protocol
- Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent.
- Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent).
- Evidence of interstitial lung disease or active noninfectious pneumonitis.
- History of organ transplant, including allogeneic stem cell transplantation.
- Known active CNS metastases and/or carcinomatous meningitis, per Section 8.2.1.1.
- Known active HAV, HBV, or HCV infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, anti–HCV, anti–HBc IgG or IgM, or HBsAg (in the absence of prior immunization).
- Active infections requiring systemic therapy, or IV antibiotic use up to 7 days before Cycle 1 Day 1. Note: If required by country or local regulations to be tested for COVID19 during screening, a participant should be excluded if they have a positive test result for SARS-CoV-2 infection until both the retest result is negative and clinical recovery is obtained.
- Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids).
- Participants with impaired cardiac function or clinically significant cardiac disease: a. New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy. b. Unstable angina pectoris. c. Acute myocardial infarction ≤ 6 months before study participation. d. Other clinically significant heart disease (ie, ≥ uncontrolled Grade 3 hypertension or high-grade conduction disturbance.)
- Participant is pregnant or breastfeeding.
- Has received a live vaccine within 28 days of Cycle 1 Day 1. Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live-attenuated vaccines and are not allowed.
- Current use of prohibited medication as specified in Section 6.6.2.
- Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v5.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 19 Jan 2021 | 5 |
 Denmark | Not Recruiting | 19 Jan 2021 | 3 |
 France | Not Recruiting | 19 Jan 2021 | 102 |
 Germany | Not Recruiting | 19 Jan 2021 | 5 |
 Italy | Not Recruiting | 19 Jan 2021 | 48 |
 Norway | Not Recruiting | 19 Jan 2021 | 5 |
 Spain | Not Recruiting | 19 Jan 2021 | 31 |
 Sweden | Not Recruiting | 19 Jan 2021 | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RetifanlimabINCMGA00012 | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 500 | 13 | PRD6569529 |
CARBOPLATINE ACCORD 10 mg/ml, solution pour perfusion | Test | SOLUTION POUR PERFUSION | INTRAVENOUS USE | 750 | 6 | PRD415297 |
Bendatax 6 mg/ ml | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 80 | 6 | PRD2957674 |
Placebo liquidnot containing the active substance, otherwise identical to INCMGA0012 | Placebo | N/A | — | — | — | N/A |