NCT04913220 - A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers (Pegathor Skin 201) | Crick

Eligibility

Sex: ALLMin age: 18 Years

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Inclusion Criteria: * Participant must be ≥18 years of age (or country's legal age of majority if \>18 years), at the time of signing the informed consent. * Participants with: * Cohort A: Histologically confirmed unresectable locally advanced or metastatic melanoma that are not amenable to local therapy * Cohort B: Histologically confirmed metastatic CSCC or locally advanced * CSCC that are not candidates for curative surgery or radiation. Special considerations for the following categories: Participants with tumors arising on the cutaneous hair (non-glabrous) bearing lip with extension onto dry red lip (vermillion) may be eligible after communication with and approval from the Sponsor Participants with the primary site is nose are only eligible if the primary site was skin, not nasal mucosa with outward extension to skin (the Investigator confirmed) Participants with mixed histology in which the predominant histology is invasive CSCC may be eligible after communication with and approval from the Sponsor * Participants in both cohorts must have at least one measurable lesion * Provision of tumor tissue: For participants in the dose escalation: 16 µg/kg: at screening, biopsy is optional but highly recommended; and on-treatment not required 24 µg/kg: at screening, biopsy is mandatory and on-treatment, optional but highly recommended * For the other participants : Mandatory baseline biopsy for the participants to enroll in cohort A with skin metastasis and in cohort B. Mandatory on-treatment biopsy for participants in Cohort A with skin metastasis and participants in Cohort B. * Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees: to use approved contraception method and submit to regular pregnancy testing prior to treatment and for at least 180 days after discontinuing study treatment and to refrain from donating or cryopreserving eggs for 180 days after discontinuing study treatment. * Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment. * Capable of giving signed informed consent Exclusion Criteria: * Participants are excluded from the study if any of the following criteria apply: * Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 * Poor organ function * Participants with baseline SpO2 ≤92% * Active brain metastases or leptomeningeal disease. * History of allogenic tissue/solid organ transplant. * Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery or local intervention within 28 days. * History of lung disease * Comorbidity requiring corticosteroid therapy * Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP * Severe or unstable cardiac condition within 6 months prior to starting study treatment * Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years * Known second malignancy either progressing or requiring active treatment within the last 3 years For both cohorts: * Prior immune checkpoint inhibitors except in the context of adjuvant or neoadjuvant; Participants who were on control arm of a study with an investigational anti-PD-1/PD-L1 are eligible. * Received adjuvant or neoadjuvant therapy during the 6 months prior to development of metastatic disease. * For Cohort A: any prior systemic treatment for advanced/metastatic disease * For Cohort B: \>2 prior lines of any systemic treatment for advanced/metastatic disease * Inability to undergo any contrast-enhanced radiologic response assessment * Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Outcomes

Primary Outcomes

All Cohorts: Objective Response Rate (ORR)

The ORR was defined as the percentage of participants who had best overall response (BOR) as confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or modified world health organization (WHO) response criteria. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From first dose of study treatment administration (Day 1) up to approximately 25 months (Cohorts A and B)

Secondary Outcomes

All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the investigator's opinion) or became serious during the TE period.

Time frame: From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 27 months (Cohorts A and B)

All Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)

Selected events that occurred during the DLT observation period were considered as DLT unless due to PD or to a cause obviously unrelated to pegenzileukin. Selected events included: any grade 4 neutropenia irrespective of duration; any febrile neutropenia; grade 3 thrombocytopenia associated with transfusion in addition to bleeding and any grade 4 thrombocytopenia; grade 3 or above: alanine aminotransferase or aspartate aminotransferase, vascular leak syndrome, hypotension, cytokine release syndrome, and AE that did not resolve to grade \<=2 within 7 days of starting accepted standard of care medical management; and grade 4 laboratory abnormalities.

Time frame: From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days: Cohorts A and B)

All Cohorts: Complete Response (CR) Rate

The CR rate was defined as the percentage of participants who had a confirmed CR as per RECIST v 1.1 or modified WHO response criteria. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm).