A Dose Optimization/Expansion Study of SAR445877 in Adult Chinese Participants With Advanced Gastric or Gastroesophageal Junction Cancer

Official title

A Phase 2, Open-label, Dose Optimization/Expansion Study of SAR445877 Administered as Monotherapy or in Combination With Other Anticancer Therapies in Adults With Advanced Gastric or Gastroesophageal Junction Cancer

Overview

This is a Phase 2, open-label, dose optimization/expansion study to assess the preliminary efficacy and safety of SAR445877 as a monotherapy for Chinese participants aged at least 18 years with advanced Gastric Cancer(GC)/Gastroesophageal Junction cancer (GEJ). Participants with advanced GC/GEJ who relapsed to at least 1 prior regimen which may or may not include an anti-PD1/PD-L1-based treatment depending on local standard of care, regardless combined positivity score (CPS) will be randomized in this study. In this study, SAR445877 will be assessed as a monotherapy in approximately 30 participants with advanced unresectable or metastatic GC or Siewert Type 2 and 3 GEJ, and for whom receiving the standard of care (SOC) is not in his or her best interest, or where no SOC is established. Human epidermal growth factor receptor 2 (HER2) positive cases will not be eligible unless they have progressed on a HER2 targeted therapy. Those participants should have received at least 1 prior line of anti-cancer treatment which may or may not include an anti-PD1/PD-L1-based treatment depending on local standard of care. Metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cases are not eligible.

Interventions

• Drug SAR445877
  Pharmaceutical form:Concentrate for solution for infusion-Route of administration:IV infusion

Primary outcome measures

• Objective response rate [Time frame: From baseline to the end of study, up to approximately 2 years]

Secondary outcome measures (11)

• maximum serum concentration (Cmax) [Time frame: Cycle 1 Day 1 to Day 14(Each cycle is 14 days)]
• time to maximum concentration (tmax) [Time frame: Cycle 1 Day 1 to Day 14(Each cycle is 14 days)]
• area under the concentration-time curve over dosing interval (AUCtau) [Time frame: Cycle 1 Day 1 to Day 14(Each cycle is 14 days)]
• End of infusion serum concentration (Cend of infusion) [Time frame: at Cycle 1 Day 1and Cycle 3 Day 1(Each cycle is 14 days)]
• Percentage of participants with presence of anti-drug antibodies (ADA) against SAR445877 [Time frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions]
• Time to response (TTR) [Time frame: From baseline to the end of study, up to approximately 2 years]
• Duration of response (DOR) [Time frame: From baseline to the end of study, up to approximately 2 years]
• Clinical benefit rate [Time frame: From baseline to the end of study, up to approximately 2 years]
• Progression-free survival (PFS) [Time frame: From baseline to the end of study, up to approximately 2 years]
• Overall survival (OS) [Time frame: From baseline to the end of study, up to approximately 2 years]
• Number of participants with presence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) [Time frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions]

Eligibility criteria

Inclusion criteria

Age

\- Participant must be at least 18 years of age inclusive (or country's legal age of majority if >18 years), at the time of signing the informed consent.

Cancer diagnosis:

• Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ.
• Participants with unknown HER2/neu status must have their HER2/neu status determined locally. Participants with HER2/neu negative are eligible. Participants with HER2/neu positive tumors must have documentation of disease progression on treatment containing an approved HER2 targeted therapy to be eligible.

Prior anticancer therapy:

\- Participants should have failed or relapsed after at least 1 prior line of treatment which may or may not include an anti-PD1/PD-L1-based treatment or anti-Claudin 18.2 based treatment depending on local standard of care.

Measurable Disease:

\- At least 1 measurable lesion per RECIST 1.1 criteria.

Exclusion criteria

Medical conditions

• Eastern Cooperative Oncology Group(ECOG)performance status of ≥2.
• Predicted life expectancy ≤3 months.
• Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment.
• Active brain metastases or leptomeningeal metastases.
• Known microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumor.
• History of treatment-related immune-mediated (or immune-related) AEs from immune- modulatory agents (including but not limited to anti-PD1/PD-L1 agents and anti cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were Grade 4 in severity, or have not resolved to Grade ≤1.
• Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or an anti-inflammatory equivalent) within 1 week prior to the first dose of the study medicine.
• Any clinically significant cardiac (including valvular) or vascular (thromboembolic disorders) disease, within 6 months prior to the first IMP administration.
• Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related AEs (irAEs).
• Has a known history or any evidence of interstitial lung disease or active, non-infectious pneumonitis within 3 years prior to the first dose of the study drug.
• Organ transplant requiring immunosuppressive treatment.
• Uncontrolled or active infection with human immunodeficiency virus (HIV ), hepatitis B, or hepatitis C infection, or has a diagnosis of immunodeficiency.

Note: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Investigational Site Number : 1560001 — Shanghai

Identifiers

NCT: NCT07692204 · TCD23644

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗