Male and female participants at least 18 years of age who have inoperable locally recurrent or metastatic Squamous Carcinoma of the Anal Canal (SCAC) not previously treated with systemic chemotherapy. MedDRA version: 20.0 Level: LLT Classification code 10002127 Term: Anal canal cancer recurrent System Organ Class: 100000004864
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to comprehend and willing to sign a written ICF for the study. 2. Are 18 years of age or older (or as applicable per local country requirements). a. Japan: Are 18 to 19 years inclusive at the time of signing the informed consent; a legally minor participant from Japan requires written parental or legal guardian's consent. 3. Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC. 4. 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. 5. 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. 6. 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. 7. ECOG performance status 0 to 1. 8. 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. 9. 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. 10. Has been fully vaccinated against SARS-CoV-2 or is willing and able to be fully vaccinated against SARS-CoV-2 during the study by starting the vaccination process (eg, with at least 1 dose of a vaccine if the vaccine consists of multiple doses) during screening. Note: See Appendix D for vaccination-related information. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjec
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Has received prior PD-(L)1 directed therapy 2. 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). 3. Participants with laboratory values at screening defined in Table 8 of the protocol 4. 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. 5. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). 6. Evidence of interstitial lung disease or active noninfectious pneumonitis. 7. History of organ transplant, including allogeneic stem cell transplantation. 8. Known active CNS metastases and/or carcinomatous meningitis, per Section 8.2.1.1. 9. 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). 10. 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. 11. Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids). 12. 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.) 13. Participant is pregnant or breastfeeding. 14. 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. 15. Current use of prohibited medication as specified in Section 6.6.2. 16. Has pre-existing peripheral neuropathy that is = Grade 2 by CTCAE v5. 17. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy (PFS) of carboplatin-paclitaxel with INCMGA00012 versus carboplatin-paclitaxel with placebo in participants with inoperable locally advanced or metastatic SCAC not previously treated with systemic chemotherapy.;Secondary Objective: To compare the efficacy (OS) of carboplatin-paclitaxel with INCMGA00012 versus carboplatin-paclitaxel with placebo in participants with inoperable locally advanced or metastatic SCAC not previously treated with systemic chemotherapy.;Primary end point(s): PFS, defined as the time from the date of randomization until disease progression according to RECIST v1.1 by BICR or death due to any cause.;Timepoint(s) of evaluation of this end point: Imaging and response assessment should be performed every 8 weeks (56 days ± 7 days) until the Week 56 assessment and then every 12 weeks (84 days ± 7 days) during the Crossover Period or Disease Follow-Up Period as appropriate until second disease progression, withdrawal of consent, death, or notification to site by the sponsor, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): OS, defined as the time from the date of randomization until death due to any cause. ORR, defined as the percentage of participants having a CR or PR, according to RECIST v1.1 as determined by BICR. DOR, defined as the time from the first documented response (CR or PR) according to RECIST v1.1 until disease progression as determined by BICR or death due to any cause. DCR, defined as the number of participants maintaining either an ORR or stable disease according to RECIST v1.1 as determined by BICR. Number of participants experiencing AEs and number of participants discontinuing study drug due to AEs.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Australia, Belgium, Denmark, France, Germany, Italy, Norway, Puerto Rico, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed