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

• ClinicalTrials.gov Identifier: NCT05013554
• Recruitment Status: Terminated
• First Posted: August 19, 2021
• Last Update Posted: February 9, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neoplasm Malignant; Breast Cancer; Lung Neoplasm Malignant; Gastric Cancer; Neoplasm	Drug: SAR443216 IV; Drug: SAR443216 SC	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: August 16, 2021
• Actual Primary Completion Date: January 15, 2024
• Actual Study Completion Date: January 15, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Part 1: Dose Escalation Determine the MTD/maximum administered dose (MAD) and RD(s) of SAR443216 [ Time Frame: Cycle 1, cycle duration is 28 days for 2-week lead-in schedule and 35 days for 3-week lead-in schedule ]
   Incidence of study dose limiting toxicities (DLTs)
2. Part 1: Dose Escalation: Safety of SAR443216 [ Time Frame: Baseline until end of study, up to approximately 7.5 months ]
   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.
3. Part 2: Dose Expansion Objective response rate (ORR) of SAR443216 in all participants [ Time Frame: From date of enrollment until the end of treatment, up to approximately 5.5 months ]
   Objective response rate is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) per RECIST v1.1.
4. Part 2: Dose Expansion Duration of response (DoR) of SAR443216 in all participants. [ Time Frame: From date of enrollment until the end of treatment, up to approximately 5.5 months ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Texas

~University of Texas - MD Anderson Cancer Center Site Number : 8400002

Houston, Texas, United States, 77030

Belgium

Investigational Site Number : 0560002

Gent, Belgium, 9000

France

Investigational Site Number : 2500001

Pierre Benite, France, 69495

Investigational Site Number : 2500002

Villejuif, France, 94800

Korea, Republic of

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, Korea, Republic of, 05505

Spain

Investigational Site Number : 7240003

Barcelona, Barcelona [Barcelona], Spain, 08035

Investigational Site Number : 7240002

Madrid / Madrid, Madrid, Comunidad De, Spain, 28050

Investigational Site Number : 7240001

Madrid, Madrid, Comunidad De, Spain, 28040

Taiwan

Investigational Site Number : 1580001

Taichung City, Taiwan, 404

Investigational Site Number : 1580002

Tainan, Taiwan, 704

Sponsors and Collaborators

Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05013554
• Other Study ID Numbers: TED16925; U1111-1253-2233 ( Registry Identifier: ICTRP ); 2023-506852-26-00 ( Registry Identifier: CTIS ); 2021-000086-32 ( EudraCT Number )
• First Posted: August 19, 2021
• Last Update Posted: February 9, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• 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

Additional relevant MeSH terms:

Neoplasms; Lung Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases