Clinical trial NCT05013554: Dose Escalation and Expansion Study of SAR443216 in Participants With Relapsed/Refractory HER2 Expressing Solid Tumors
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasm Malignant
Breast Cancer
Lung Neoplasm Malignant
Gastric Cancer
Neoplasm
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-08-19
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Part 1: Dose Escalation Determine the MTD/maximum administered dose (MAD) and RD(s) of SAR443216
timeFrame: Cycle 1, cycle duration is 28 days for 2-week lead-in schedule and 35 days for 3-week lead-in schedule
measure: Part 1: Dose Escalation: Safety of SAR443216
timeFrame: Baseline until end of study, up to approximately 7.5 months
measure: Part 2: Dose Expansion Objective response rate (ORR) of SAR443216 in all participants
timeFrame: From date of enrollment until the end of treatment, up to approximately 5.5 months
measure: Part 2: Dose Expansion Duration of response (DoR) of SAR443216 in all participants.
timeFrame: From date of enrollment until the end of treatment, up to approximately 5.5 months
Secondary outcomes:
measure: Part 1: Objective response rate (ORR) of SAR443216 in all participants
timeFrame: From date of enrollment until the end of treatment, up to approximately 3.5 months
measure: Part 1: Duration of response (DoR) of SAR443216 in all participants
timeFrame: From date of enrollment until the end of treatment, up to approximately 3.5 months
measure: Part 1 and Part 2: Progression Free Survival (PFS)
timeFrame: From date of enrollment until the end of treatment, up to approximately 3.5 months for Part1 and 5.5 months for Part 2
measure: Part 2: Safety of SAR443216
timeFrame: Baseline until the end of the study, up to approximately 9.5 months
measure: Part 1 and Part 2: Pharmacokinetic Parameter: Cmax of SAR443216
timeFrame: 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
measure: Part 1 and Part 2: Pharmacokinetic Parameter: Ctrough of SAR443216
timeFrame: 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
measure: Part 1 and Part 2: Pharmacokinetic Parameter: t 1/2 of SAR443216
timeFrame: 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
measure: Part 1 and Part 2: Pharmacokinetic Parameter: AUC0-τ of SAR443216
timeFrame: 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
measure: Part 1 and Part 2: Evaluation of SAR443216 immunogenicity
timeFrame: 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
Other outcomes:
Locations:
city: Houston
country: United States
facility: ~University of Texas - MD Anderson Cancer Center Site Number : 8400002
state: Texas
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500001
city: Villejuif
country: France
facility: Investigational Site Number : 2500002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
state: Madrid, Comunidad De
city: Taichung City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580002
Study officials:
References: