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

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.

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.

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.

Participants with metastatic breast cancers with HER2 high expression (with amplification) will receive SAR443216 as intravenous (IV) infusion.

Participants with metastatic breast cancers with HER2 low expression or HER2 mutation (without amplification) will receive SAR443216 as intravenous (IV) infusion.

Participants with metastatic gastric cancers with HER2 low expression or HER2 mutation (without amplification) will receive SAR443216 as intravenous (IV) infusion.

Participants with metastatic NSCLC with HER2 low or high expression and/or HER2 mutation will receive SAR443216 as intravenous (IV) infusion.

Cycle 1, cycle duration is 28 days for 2-week lead-in schedule and 35 days for 3-week lead-in schedule

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.

Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.

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.

Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.

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

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

Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and lab abnormalities according to NCI CTCAE Version 5.0

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

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

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

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

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

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.

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