Clinical trial NCT04913220: A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers (Pegathor Skin 201)
Official title: A Phase 1/2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR- 707) Combined With Cemiplimab for the Treatment of Participants With Advanced Unresectable or Metastatic Skin Cancers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Malignant Melanoma
Squamous Cell Carcinoma of Skin
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-06-04
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

-To determine the antitumor activity of SAR444245 in combination with cemiplimab.

Secondary Objectives:

* To determine the recommended phase 2 dose and to assess the safety profile of SAR444245 when combined with cemiplimab
* To assess other indicators of antitumor activity
* To assess the concentrations of SAR444245 when given in combination with cemiplimab
* To assess the immunogenicity of SAR444245
* To assess active concentrations of cemiplimab when given in combination with SAR444245

Detailed description: The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 28 days, a treatment period \[max 35 cycles or until PD\], an end-of-treatment visit 30 days + 7 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or final cohort cut-off, whichever is earlier

Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) in Cohort A (melanoma)
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximatively 9 months after the last participant receive first dose.
measure: Objective response rate (ORR) in Cohort B (CSCC)
timeFrame: Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximatively 9 months after the last participant receive first dose.
Secondary outcomes:
measure: Phase 2 dose determination
timeFrame: The observation period is 1 cycle (21 days)
measure: Assessment of SAR444245 safety profile when combined with cemiplimab-Treatment Emergent Adverse Events
timeFrame: From 1st IMP dose up to 30 days after the last dose of IMP
measure: Assessment of SAR444245 safety profile when combined with cemiplimab-Serious Adverse Events
timeFrame: From 1st IMP dose up to 90 days after the last dose of IMP
measure: Complete Response rate
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Time to Complete Response
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Time to Response
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Duration of Response (DoR)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Clinical Benefit Rate (CBR)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Progression Free Survival (PFS)
timeFrame: From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
measure: Concentration of SAR444245
timeFrame: At Day1, Day2, Day3 of Cycle1 and Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months
measure: Incidence of anti-drug antibodies (ADAs) against SAR444245
timeFrame: At Day1 and Day 15 of Cycle1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum is up to approximately 24 months.
measure: C trough of cemiplimab
timeFrame: Day 1 of Cycle 1-2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after the last IMP administration, maximum is up to approximately 24 months.
measure: C end_of_Infusion of cemiplimab
timeFrame: Day 1 of Cycle 1-2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center & Optima Diagnostic Imaging Site Number : 8400007
state: California
city: Macquarie University
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Santaigo
country: Chile
facility: Investigational Site Number : 1520005
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Antofagasta
country: Chile
facility: Investigational Site Number : 1520006
city: Temuco
country: Chile
facility: Investigational Site Number : 1520003
city: Bobigny
country: France
facility: Investigational Site Number : 2500003
city: Dijon
country: France
facility: Investigational Site Number : 2500002
city: Lille
country: France
facility: Investigational Site Number : 2500005
city: Nantes
country: France
facility: Investigational Site Number : 2500001
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500006
city: Berlin
country: Germany
facility: Investigational Site Number : 2760004
city: Hamburg
country: Germany
facility: Investigational Site Number : 2760001
city: Mannheim
country: Germany
facility: Investigational Site Number : 2760003
city: Minden
country: Germany
facility: Investigational Site Number : 2760006
city: München
country: Germany
facility: Investigational Site Number : 2760005
city: Napoli
country: Italy
facility: Investigational Site Number : 3800001
city: Perugia
country: Italy
facility: Investigational Site Number : 3800004
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Investigational Site Number : 7240002
state: Cantabria
Study officials:
References: