Gastric Cancer, Oesophageal Carcinoma
Conditions
Brief summary
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
DRUGSAR445877
Pharmaceutical form:Concentrate for solution for infusion-Route of administration:IV infusion
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | From baseline to the end of study, up to approximately 2 years | Objective response rate, which is defined as the proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| maximum serum concentration (Cmax) | Cycle 1 Day 1 to Day 14(Each cycle is 14 days) | — |
| time to maximum concentration (tmax) | Cycle 1 Day 1 to Day 14(Each cycle is 14 days) | — |
| area under the concentration-time curve over dosing interval (AUCtau) | Cycle 1 Day 1 to Day 14(Each cycle is 14 days) | — |
| End of infusion serum concentration (Cend of infusion) | 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 | From the first dose of Cycle 1 to 30 days after last dose of study interventions | — |
| Time to response (TTR) | From baseline to the end of study, up to approximately 2 years | Time to response (TTR), defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of confirmed partial response (PR) or complete response (CR) determined by Investigator per RECIST v1.1 |
| Duration of response (DOR) | From baseline to the end of study, up to approximately 2 years | Duration of response (DOR), defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) determined by Investigator per RECIST v1.1 or death from any cause, whichever occurs first |
| Clinical benefit rate | From baseline to the end of study, up to approximately 2 years | Clinical benefit rate including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator per RECIST v1.1 |
| Progression-free survival (PFS) | From baseline to the end of study, up to approximately 2 years | Progression-free survival (PFS), defined as the time from the date of first administration of IMP to the date of the first documented disease progression determined by Investigator as per RECIST v1.1 or death from any cause, whichever occurs first |
| Overall survival (OS) | From baseline to the end of study, up to approximately 2 years | Overall survival (OS), defined as the time from the first dose of IMP to the date of death due to any cause |
| Number of participants with presence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) | The time from the first dose of study interventions up to 30 days after last dose of study interventions | — |
Countries
China
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed