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

Malignant Melanoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04913220
• Other study ID #: ACT16845
• Secondary ID: U1111-1254-01892
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 15, 2021
• Est. completion date: February 11, 2025

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: February 11, 2025
• Est. primary completion date: August 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma
• Skin Neoplasms
• Squamous Cell Carcinoma of Skin

Intervention

Drug:
• THOR-707
Solution for infusion: intravenous infusion
• Cemiplimab
Solution for infusion: intravenous infusion

Locations

Country	Name	City	State
Australia	Investigational Site Number : 0360001	Macquarie University	New South Wales
Chile	Investigational Site Number : 1520006	Antofagasta
Chile	Investigational Site Number : 1520005	Santaigo	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520004	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Temuco
France	Investigational Site Number : 2500003	Bobigny
France	Investigational Site Number : 2500002	Dijon
France	Investigational Site Number : 2500005	Lille
France	Investigational Site Number : 2500001	Nantes
France	Investigational Site Number : 2500006	Pierre Benite
Germany	Investigational Site Number : 2760004	Berlin
Germany	Investigational Site Number : 2760001	Hamburg
Germany	Investigational Site Number : 2760003	Mannheim
Germany	Investigational Site Number : 2760006	Minden
Germany	Investigational Site Number : 2760005	München
Italy	Investigational Site Number : 3800001	Napoli
Italy	Investigational Site Number : 3800004	Perugia
Spain	Investigational Site Number : 7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240002	Santander	Cantabria
United States	Beverly Hills Cancer Center & Optima Diagnostic Imaging Site Number : 8400007	Beverly Hills	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Chile,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) in Cohort A (melanoma)	Cohort A (melanoma): Objective response rate (ORR) defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) determined by investigator per response evaluation criteria in solid tumors (RECIST) 1.1.	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.
Primary	Objective response rate (ORR) in Cohort B (CSCC)	Cohort B (CSCC): ORR defined as the proportion of participants who have a confirmed CR or PR determined by investigator per RECIST 1.1, or modified WHO criteria for medical photographs of external skin lesions, or composite criteria.	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	Phase 2 dose determination	Incidence of Dose-limiting toxicities (DLTs) during DLT observation period	The observation period is 1 cycle (21 days)
Secondary	Assessment of SAR444245 safety profile when combined with cemiplimab-Treatment Emergent Adverse Events	Incidence of treatment-emergent adverse event (TEAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings	From 1st IMP dose up to 30 days after the last dose of IMP
Secondary	Assessment of SAR444245 safety profile when combined with cemiplimab-Serious Adverse Events	Incidence of serious-adverse events (SAEs) and laboratory abnormalities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings	From 1st IMP dose up to 90 days after the last dose of IMP
Secondary	Complete Response rate	Complete Response rate (CRR) defined as the proportion of participants who have a confirmed CR determined by the Investigator per RECIST 1.1 for melanoma participants and when applicable for CSCC participants (CR in localized unresectable CSCC is exploratory)	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
Secondary	Time to Complete Response	Time to CR defined as the time from the first administration of IMP to the first tumor assessment at which the overall response was CR that is subsequently confirmed and determined by Investigator per RECIST 1.1 for melanoma participants and when applicable for CSCC participants	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
Secondary	Time to Response	Time to Response (TTR), defined as the time from first administration of IMP to the first tumor assessment at which the overall response was CR or PR that is subsequently confirmed and determined by Investigator per RECIST 1.1 or modified WHO Criteria or composite criteria whichever relevant	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
Secondary	Duration of Response (DoR)	Duration of Response (DoR), defined as the time from first tumor assessment at which the overall response was CR or PR that is subsequently confirmed until documented progressive disease (PD) determined by Investigator per RECIST 1.1 or modified WHO Criteria for medical photographs or composite criteria when relevant, or death from any cause, whichever occurs first	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
Secondary	Clinical Benefit Rate (CBR)	Clinical Benefit Rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months (determined by Investigator per RECIST 1.1 or modified WHO criteria for medical photographs or composite criteria whichever relevant).	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
Secondary	Progression Free Survival (PFS)	Progression Free Survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator per RECIST 1.1, or modified WHO Criteria for medical photographs when relevant or death due to any cause, whichever occurs first.	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
Secondary	Concentration of SAR444245		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
Secondary	Incidence of anti-drug antibodies (ADAs) against SAR444245		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.
Secondary	C trough of cemiplimab	Concentration observed just before treatment administration during repeated dosing (C trough)	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.
Secondary	C end_of_Infusion of cemiplimab	The concentration observed just after the end of infusion	Day 1 of Cycle 1-2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months.