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

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05013554
• Other study ID #: TED16925
• Secondary ID: U1111-1253-22332
• Status: Terminated
• Phase: Phase 1
• Start date: August 16, 2021
• Est. completion date: January 15, 2024

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: January 15, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Gastric Cancer
• Lung Neoplasm Malignant
• Lung Neoplasms
• Neoplasm
• Neoplasm Malignant
• Neoplasms

Intervention

Drug:
• SAR443216 IV
Pharmaceutical form: Powder for solution; Route of administration: IV infusion
• SAR443216 SC
Pharmaceutical form: Powder for solution; Route of administration: SC injection

Locations

Country	Name	City	State
Belgium	Investigational Site Number : 0560002	Gent
France	Investigational Site Number : 2500001	Pierre Benite
France	Investigational Site Number : 2500002	Villejuif
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Spain	Investigational Site Number : 7240003	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Madrid	Madrid, Comunidad De
Spain	Investigational Site Number : 7240002	Madrid / Madrid	Madrid, Comunidad De
Taiwan	Investigational Site Number : 1580001	Taichung City
Taiwan	Investigational Site Number : 1580002	Tainan
United States	~University of Texas - MD Anderson Cancer Center Site Number : 8400002	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  France,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1 and Part 2: Pharmacokinetic Parameter: t 1/2 of SAR443216	Terminal half-life associated with the terminal slope (?z)	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
Secondary	Part 1 and Part 2: Pharmacokinetic Parameter: AUC0-t 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
Secondary	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