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

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

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

Study Overview

• Status: Terminated
• Conditions: Malignant Melanoma; Squamous Cell Carcinoma of Skin
• Intervention / Treatment: Drug: THOR-707; Drug: Cemiplimab

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

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Macquarie University, New South Wales, Australia, 2109
      • Investigational Site Number : 0360001
• Chile
  • Antofagasta, Chile, 1420000
    • Investigational Site Number : 1520006
  • Temuco, Chile, 4800827
    • Investigational Site Number : 1520003
  • Reg Metropolitana de Santiago
    • Santaigo, Reg Metropolitana de Santiago, Chile, 8241470
      • Investigational Site Number : 1520005
    • Santiago, Reg Metropolitana de Santiago, Chile, 8420383
      • Investigational Site Number : 1520001
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500921
      • Investigational Site Number : 1520002
    • Santiago, Reg Metropolitana de Santiago, Chile
      • Investigational Site Number : 1520004
• France
  • Bobigny, France, 93009
    • Investigational Site Number : 2500003
  • Dijon, France, 21079
    • Investigational Site Number : 2500002
  • Lille, France, 59037
    • Investigational Site Number : 2500005
  • Nantes, France, 44093
    • Investigational Site Number : 2500001
  • Pierre-Bénite, France, 69495
    • Investigational Site Number : 2500006
• Germany
  • Berlin, Germany, 10117
    • Investigational Site Number : 2760004
  • Hamburg, Germany, 20246
    • Investigational Site Number : 2760001
  • Mannheim, Germany, 68167
    • Investigational Site Number : 2760003
  • Minden, Germany, 32429
    • Investigational Site Number : 2760006
  • München, Germany, 80337
    • Investigational Site Number : 2760005
• Italy
  • Napoli, Italy, 80131
    • Investigational Site Number : 3800001
  • Perugia, Italy, 06126
    • Investigational Site Number : 3800004
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240001
    • Barcelona, Barcelona [Barcelona], Spain, 08036
      • Investigational Site Number : 7240004
    • L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain, 08908
      • Investigational Site Number : 7240003
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Investigational Site Number : 7240002
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center & Optima Diagnostic Imaging Site Number : 8400007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Melanoma; SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.	Drug: THOR-707; Solution for infusion: intravenous infusion; Drug: Cemiplimab; Solution for infusion: intravenous infusion; Other Names: Libtayo® or generic
Experimental: Cohort B: cutaneous squamous cell carcinoma (CSCC); SAR444245 and cemiplimab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.	Drug: THOR-707; Solution for infusion: intravenous infusion; Drug: Cemiplimab; Solution for infusion: intravenous infusion; Other Names: Libtayo® or generic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study treatment administration (Day 1) up to approximately 25 months (Cohorts A and B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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).	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Time to Complete Response	The time to CR was defined as the time from the first administration of study treatment to the first tumor assessment at which the overall response was recorded as CR that was subsequently confirmed 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).	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Time to Response (TTR)	The TTR was defined as the time from the first study treatment administration to the first tumor assessment at which the overall response was recorded as PR or CR that was subsequently confirmed 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). 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.	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Duration of Response (DOR)	The DOR was defined as the time from the first tumor assessment at which the overall response was recorded as CR or PR that was subsequently confirmed until documented PD before the initiation of any subsequent anti-cancer therapy or death due to any cause, whichever occurred first, 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). 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. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Clinical Benefit Rate (CBR)	The CBR was defined as the percentage of participants with clinical benefit: confirmed CR or PR as BOR, or stable disease (SD) lasting at least 6 months, 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). 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. BOR was defined as the best response observed from the start of the study treatment until PD, death, cut-off date or initiation of post-treatment anti-cancer therapy, whichever occurred first. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Progression Free Survival (PFS)	The PFS was defined as the time from the date of first study treatment administration to the date of the first documentation of objective PD, or death due to any cause, whichever occurred first, as per RECIST v 1.1 or modified WHO response criteria. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).	From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment, approximately 26 months (Cohorts A and B)
All Cohorts: Plasma Concentrations of Pegenzileukin	Blood samples were collected at specified timepoints for the assessment of plasma concentrations of pegenzileukin.	Cycle 1 Days 2 and 3 (each cycle is 21 days)
All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin	Blood samples were collected at specified timepoints to assess the presence of ADAs against pegenzileukin. Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA is presented.	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: Concentration Observed Just Before Study Treatment Administration During Repeated Dosing (Ctrough) of Cemiplimab	Blood samples were collected at specified timepoints for the assessment of Ctrough of cemiplimab. The PK population consisted of all participants from exposed population with at least one PK concentration available after the first dose of study treatment. Only participants with data collected at specified timepoints are reported.	Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days)
All Cohorts: Concentration at End of Infusion (Ceoi) of Cemiplimab	Blood samples were collected at specified timepoints for the assessment of Ceoi of cemiplimab. The PK population consisted of all participants from exposed population with at least one PK concentration available after the first dose of study treatment. Only participants with data collected at specified timepoints are reported.	Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• ACT16845 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): February 18, 2025

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 4, 2021

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Pharmaceutical Preparations; cemiplimab; Drugs, Generic
• Other Study ID Numbers: ACT16845; U1111-1254-0189 (Registry Identifier: ICTRP); 2020-005332-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No