Breast Cancer, Gastric Cancer, Lung Neoplasm Malignant, Neoplasm, Neoplasm Malignant
Conditions
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.
Interventions
DRUGSAR443216 IV
Pharmaceutical form: Powder for solution; Route of administration: IV infusion
DRUGSAR443216 SC
Pharmaceutical form: Powder for solution; Route of administration: SC injection
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Dose Escalation Determine the MTD/maximum administered dose (MAD) and RD(s) of SAR443216 | 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) |
| Part 1: Dose Escalation: Safety of SAR443216 | 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. |
| Part 2: Dose Expansion Objective response rate (ORR) of SAR443216 in all participants | 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. |
| Part 2: Dose Expansion Duration of response (DoR) of SAR443216 in all participants. | 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
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Pharmacokinetic Parameter: Cmax of SAR443216 | 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 |
| Part 1 and Part 2: Pharmacokinetic Parameter: Ctrough of SAR443216 | 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 |
| Part 1: Objective response rate (ORR) of SAR443216 in all participants | 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. |
| Part 1 and Part 2: Pharmacokinetic Parameter: AUC0-τ of SAR443216 | 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 |
| Part 1 and Part 2: Evaluation of SAR443216 immunogenicity | 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 |
| Part 1 and Part 2: Pharmacokinetic Parameter: t 1/2 of SAR443216 | 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) |
| Part 1: Duration of response (DoR) of SAR443216 in all participants | 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 |
| Part 1 and Part 2: Progression Free Survival (PFS) | 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 |
| Part 2: Safety of SAR443216 | 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 |
Countries
Belgium, France, South Korea, Spain, Taiwan, United States
Outcome results
None listed