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

Sanofi

Status and phase: Terminated; Phase 1

Conditions: Neoplasm; Breast Cancer; Gastric Cancer; Lung Neoplasm Malignant; Neoplasm Malignant

Treatments: Drug: SAR443216 SC; Drug: SAR443216 IV

Study type: Interventional

Funder types: Industry

Identifiers

NCT05013554

TED16925

2021-000086-32 (EudraCT Number)

U1111-1253-2233 (Registry Identifier)

2023-506852-26-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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44 participants in 5 patient groups

SAR443216-Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: SAR443216 IV

Drug: SAR443216 SC

SAR443216-Dose Expansion - metastatic breast cancers with HER2 high expression: Cohort A

Experimental group

Description:

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

Treatment:

Drug: SAR443216 IV

SAR443216-Dose Expansion- metastatic breast cancers with HER2 low expression: Cohort B

Experimental group

Description:

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

Treatment:

Drug: SAR443216 IV

SAR443216-Dose Expansion- metastatic gastric cancers with HER2 low expression: Cohort C

Experimental group

Description:

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

Treatment:

Drug: SAR443216 IV

SAR443216-Dose Expansion - metastatic NSCLC with HER2 low or high expression: Cohort D

Experimental group

Description:

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

Treatment:

Drug: SAR443216 IV