Dose Escalation and Expansion Study of SAR444200-based Regimen in Adult Participants With Advanced Solid Tumors

A Phase 1/2 Open-label, First-in-human, Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR444200-based Regimen in Participants With Advanced Solid Tumors.

This is Phase 1/Phase 2, open label, multiple cohort, first-in-human study to evaluate safety, PK, PDy and efficacy of SAR444200 as a monotherapy or in combination with other anti-cancer agents for participants aged at least 18 years with previously treated metastatic malignancies.

Study Overview

• Status: Terminated
• Conditions: Neoplasm
• Intervention / Treatment: Biological: SAR444200; Biological: Atezolizumab

Detailed Description

Treatment Period: enrolled participants will receive continuous treatment until disease progression (PD), unacceptable adverse event (AE), or other permanent discontinuation criteria.

The End of Treatment visit will occur 30 days ±7 days from last IMP administration or prior to initiation of further therapy, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Investigational Site Number : 1240002
  • Quebec
    • Québec, Quebec, Canada, G1R 2J6
      • Investigational Site Number : 1240001
• China
  • Shanghai, China, 200120
    • Investigational Site Number : 1560001
  • Wuhan, China, 430022
    • Investigational Site Number : 1560002
• Singapore
  • Singapore, Singapore, 119074
    • Investigational Site Number : 7020002
  • Singapore, Singapore, 308433
    • Investigational Site Number : 7020001
  • Singapore, Singapore, 169610
    • Investigational Site Number : 7020003
• South Korea
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 05505
      • Investigational Site Number : 4100002
    • Seoul, Seoul-teukbyeolsi, South Korea, 06351
      • Investigational Site Number : 4100001
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center- Site Number : 8400004
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai- Site Number : 8400005
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Corporation- Site Number : 8400002
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center- Site Number : 8400003

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Cancer diagnosis for participants for Part 1A and Part 1B:

  1. Metastatic and/or unresectable HCC diagnosed by histology and/or cytology, or diagnosed clinically by the American Association for the Study of Liver Diseases (AASLD) criteria for participants with liver cirrhosis (participants without liver cirrhosis must be diagnosed histologically) OR Other histology/cytology proven advanced and/or metastatic non-HCC solid tumors
  2. Not amenable to available standard of care: participants must have experienced disease progression on/after standard of care, or no acceptable standard curative or palliative treatments exist (or are no longer effective), according to Investigator judgement, or the participant declines standard of care therapy.

• Cancer diagnosis for participants for Part 2A:

  1. Metastatic NSCLC with no actionable driver gene mutants (such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)), diagnosed by histology and/or cytology not amenable to available standard of care and must have progressed on/after therapy that included an anti-PD(L)-1 agent with or without platinum-based chemotherapy.
  2. Progressive disease should be observed during the course of anti-PD(L)-1 therapy or within 12 weeks from the last dose of anti-PD(L)-1 therapy
• Additional for Part 2A: At least 1 measurable lesion per RECIST 1.1 criteria

• For all participants:

  1. Positive GPC3 expression on tumor tissue as determined locally or centrally
  2. Capable of giving signed informed consent

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.
• Predicted life expectancy ≤3 months.
• For participants with HCC: Child Pugh Class B or C liver score within 14 days of initiation of IMP. Participants with Child Pugh Class B-7 score are allowed for Part 1A.
• Known active brain metastases or leptomeningeal metastases.
• History of allogenic or solid organ transplant
• Treatment-related immune-mediated (or immune-related) AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents and anti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were Grade 4 in severity
• Significant cardiovascular disease within 3 months prior to initiation of IMP, uncontrolled arrhythmia requiring medication, or unstable angina.
• Ongoing AEs caused by any prior anti-cancer therapy >Grade 2
• Known uncontrolled human immunodeficiency virus (HIV), hepatitis B infection, or known untreated current hepatitis C infection
• Known second malignancy either progressing or requiring active treatment within the last year.
• For combination therapy: Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events
• Receipt of a live-virus vaccination within 28 days of planned treatment start.
• For Part 2A, has received prior GPC3 targeted anticancer treatment.
• Current pneumonitis or interstitial lung disease, or history of interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a participant'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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR444200 - Dose Escalation Phase (Part 1A); SAR444200 will be administered as intravenous injection as monotherapy in participants with GPC3+ solid tumors over a 21-day cycle	Biological: SAR444200; Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion
Experimental: SAR444200 - Dose Expansion Phase (Part 2A); SAR444200 will be administered as intravenous injection in participants with GPC3+ NSCLC over a 21-day cycle	Biological: SAR444200; Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion
Experimental: SAR444200 and Atezolizumab combination therapy - Dose Escalation Phase (Part 1B); SAR444200 in combination with atezolizumab will be administered as intravenous injection in participants with GPC3+ solid tumors over a 21-day cycle	Biological: SAR444200; Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion; Biological: Atezolizumab; concentrate for solution for infusion Route of administration: intravenous (IV) infusion; Other Names: Tecentriq®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1A and 1B: Number of participants with Adverse Events (AEs)	Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	the time from the first dose of study interventions up to 30 days after last dose of study interventions
Part 2A: Objective Response Rate (ORR)	ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	From baseline to the end of expansion study (up to 2 years)
Part 1A and 1B: Number of participants with Dose Limiting Toxicities (DLTs)	Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	For Part 1A: from the Cycle 1, Day 1 up to Day 21For Part 1B: from Cycle 2 Day 1 up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1A and 1B: Objective Response Rate (ORR)	ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Baseline to end of dose escalation study (up to 2 years)
All parts: Assessment of PK parameters: Cmax	Maximum plasma concentration observed	Cycle 1 Day 1 to Day 21
All parts:Assessment of PK parameters: AUC0-T	Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)	Cycle 1 Day 1to Day 21
All parts: Assessment of PK parameters: Tmax	Time to reach Cmax	Cycle 1 Day 1to Day 21
Part 2A: Progression Free Survival (PFS)	PFS, defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 (or death due to any cause, whichever occurs first)	From baseline to end of expansion study (up to 2 years)
Part 2A: Number of participants with Adverse Events (AEs)	Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	The time from the first dose of study interventions up to 30 days after last dose of study interventions.
All parts: Duration of response (DoR)	DoR defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) or death from any cause, whichever occurs first determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Baseline to end of study (up to 2 years)
All parts: Incidence of anti-drug antibodies (ADAs) to SAR444200	Incidence of participants with anti-drug antibodies to SAR444200	From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
All parts: Incidence of anti-drug antibodies (ADAs) to atezolizumab		From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• TCD17240 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Actual): December 22, 2025
• Study Completion (Actual): December 22, 2025

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab
• Other Study ID Numbers: TCD17240; U1111-1264-3207 (Registry Identifier: ICTRP); 2021-006623-17 (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