Dose Escalation and Expansion Study of SAR443216 in Participants With Relapsed/Refractory HER2 Expressing Solid Tumors

A Phase 1/1b Open-label, First-in-human, Single Agent, Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR443216 in Participants With Relapsed/Refractory HER2 Expressing Solid Tumors.

Primary Objectives:

Part 1 (Dose Escalation)

• To determine the MTD/maximum administered dose (MAD) of SAR443216 administered as a single agent in participants with HER2 expressing solid tumors and determine the RD(s) for intravenous (IV) and subcutaneous (SC) administration in the dose escalation part.
• To determine the safety of SAR443216 after intravenous (IV) and subcutaneous (SC) administration.

Part 2 (Dose expansion)

• To assess preliminary clinical activity of single agent SAR443216 at the RD(s) in participants with HER2 expressing solid tumors, with various levels of HER2 expression.

Secondary Objectives:

Part 1 • To assess preliminary clinical activity of single agent SAR443216 after IV and SC administration at the RD(s) in participants with HER2 expressing solid tumors, with various levels of HER2 expression.

Part 2

• To determine the safety of SAR443216.

Part 1 and 2

• To characterize the pharmacokinetic (PK) profile of SAR443216 when administered as a single agent after IV and SC (Part 1 only) administration.
• To evaluate the immunogenicity of SAR443216 after IV and SC administration.
• To assess preliminary clinical activity of single agent SAR443216 at the RD(s) in participants with HER2 expressing solid tumors, with various levels of HER2 expression.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Gastric Cancer; Neoplasm; Lung Neoplasm Malignant; Neoplasm Malignant
• Intervention / Treatment: Drug: SAR443216 IV; Drug: SAR443216 SC

Detailed Description

The expected duration of study intervention for participants may vary, based on progression date; median expected duration of study per participant is estimated to be:

• 7.5 months (up to 1 month for screening, a median of 3.5 months for treatment, and a median of 3 months for long term follow-up) in escalation.
• 9.5 months (up to 1 month for screening, a median of 5.5 months for treatment, and a median of 3 months for long term follow-up) in expansion.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Investigational Site Number : 0560002
• France
  • Pierre-Bénite, France, 69495
    • Investigational Site Number : 2500001
  • Villejuif, France, 94800
    • Investigational Site Number : 2500002
• South Korea
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 03080
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, South Korea, 05505
      • Investigational Site Number : 4100002
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240003
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28040
      • Investigational Site Number : 7240001
    • Madrid / Madrid, Madrid, Comunidad de, Spain, 28050
      • Investigational Site Number : 7240002
• Taiwan
  • Taichung, Taiwan, 404
    • Investigational Site Number : 1580001
  • Tainan City, Taiwan, 704
    • Investigational Site Number : 1580002
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • ~University of Texas - MD Anderson Cancer Center Site Number : 8400002

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must be ≥ 18 years of age
• Histologically or cytologically confirmed diagnosis of metastatic solid tumors
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• All participants should have at least 1 measurable disease per RECIST v1.1. An irradiated lesion can be considered measurable only if progression has been demonstrated on the irradiated lesion.
• Body weight within [45 - 150 kg] (inclusive)
• All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent

Exclusion Criteria:

• Any clinically significant cardiac disease
• History of or current interstitial lung disease or pneumonitis
• Uncontrolled or unresolved acute renal failure
• Prior solid organ or hematologic transplant.
• Known positivity with human immunodeficiency virus (HIV), known active hepatitis A, B, and C, or uncontrolled chronic or ongoing infectious requiring parenteral treatment.
• Receipt of a live-virus vaccination within 28 days of planned treatment start
• Participation in a concurrent clinical study in the treatment period.
• Inadequate hematologic, hepatic and renal function
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions.

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR443216-Dose Escalation; Participants with metastatic solid tumors that express HER2 in tumor tissue and/or with HER2 aberration will receive SAR443216 as intravenous (IV) infusion or subcutaneous (SC) injection.	Drug: SAR443216 IV; Pharmaceutical form: Powder for solution; Route of administration: IV infusion; Drug: SAR443216 SC; Pharmaceutical form: Powder for solution; Route of administration: SC injection
Experimental: SAR443216-Dose Expansion - metastatic breast cancers with HER2 high expression: Cohort A; Participants with metastatic breast cancers with HER2 high expression (with amplification) will receive SAR443216 as intravenous (IV) infusion.	Drug: SAR443216 IV; Pharmaceutical form: Powder for solution; Route of administration: IV infusion
Experimental: SAR443216-Dose Expansion- metastatic breast cancers with HER2 low expression: Cohort B; Participants with metastatic breast cancers with HER2 low expression or HER2 mutation (without amplification) will receive SAR443216 as intravenous (IV) infusion.	Drug: SAR443216 IV; Pharmaceutical form: Powder for solution; Route of administration: IV infusion
Experimental: SAR443216-Dose Expansion- metastatic gastric cancers with HER2 low expression: Cohort C; Participants with metastatic gastric cancers with HER2 low expression or HER2 mutation (without amplification) will receive SAR443216 as intravenous (IV) infusion.	Drug: SAR443216 IV; Pharmaceutical form: Powder for solution; Route of administration: IV infusion
Experimental: SAR443216-Dose Expansion - metastatic NSCLC with HER2 low or high expression: Cohort D; Participants with metastatic NSCLC with HER2 low or high expression and/or HER2 mutation will receive SAR443216 as intravenous (IV) infusion.	Drug: SAR443216 IV; Pharmaceutical form: Powder for solution; Route of administration: IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Dose Escalation: Safety of SAR443216	Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and lab abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	Baseline until end of study, up to approximately 7.5 months
Part 2: Dose Expansion Objective response rate (ORR) of SAR443216 in all participants	Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.	From date of enrollment until the end of treatment, up to approximately 5.5 months
Part 2: Dose Expansion Duration of response (DoR) of SAR443216 in all participants.	Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.	From date of enrollment until the end of treatment, up to approximately 5.5 months
Part 1: Dose Escalation Determine the MTD/maximum administered dose (MAD) and RD(s) of SAR443216	Incidence of study dose limiting toxicities (DLTs)	Cycle 1, cycle duration is 28 days for 2-week lead-in schedule and 35 days for 3-week lead-in schedule

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective response rate (ORR) of SAR443216 in all participants	Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.	From date of enrollment until the end of treatment, up to approximately 3.5 months
Part 1: Duration of response (DoR) of SAR443216 in all participants	Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first	From date of enrollment until the end of treatment, up to approximately 3.5 months
Part 1 and Part 2: Progression Free Survival (PFS)	Progression free survival (PFS) will be assessed by the Investigator per RECIST v1.1 and will be summarized using the Kaplan-Meier method	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part1 and 5.5 months for Part 2
Part 2: Safety of SAR443216	Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and lab abnormalities according to NCI CTCAE Version 5.0	Baseline until the end of the study, up to approximately 9.5 months
Part 1 and Part 2: Pharmacokinetic Parameter: Cmax of SAR443216	Maximum observed plasma concentration	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part 1 and 5.5 months for Part 2
Part 1 and Part 2: Pharmacokinetic Parameter: Ctrough of SAR443216	Plasma concentration observed just before treatment administration during repeated dosing	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part 1 and 5.5 months for Part 2
Part 1 and Part 2: Pharmacokinetic Parameter: AUC0-τ of SAR443216	Area under the plasma concentration versus time curve	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part 1 and 5.5 months for Part 2
Part 1 and Part 2: Evaluation of SAR443216 immunogenicity	Incidence of ADA induction and ADA persistence	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part 1 and 5.5 months for Part 2
Part 1 and Part 2: Pharmacokinetic Parameter: t 1/2 of SAR443216	Terminal half-life associated with the terminal slope (λz)	From date of enrollment until the end of treatment, up to approximately 3.5 months for Part 1 and 5.5 months for Part 2

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• TED16925 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): January 15, 2024

Study Registration Dates

• First Submitted: August 12, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Neoplasms; Stomach Neoplasms; Lung Neoplasms; Breast Neoplasms
• Other Study ID Numbers: TED16925; U1111-1253-2233 (Registry Identifier: ICTRP); 2021-000086-32 (EudraCT Number); 2023-506852-26-00 (Registry Identifier: CTIS)

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
• product manufactured in and exported from the U.S.: No