A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

Brief description of study

This is a Phase 1/2, open label, multiple cohort study to assess the safety and preliminary efficacy of SAR445877 as a monotherapy for participants aged at least 18 years with advanced unresectable or metastatic malignancies.

The study will include 2 parts:

A dose escalation Part 1: for finding the recommended dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW).

A multicohort dose expansion Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy (2 dose levels will be tested in at least 1 indication as applicable).

Approximately 240 participants will be enrolled to the study intervention:

For Part 1: approximately 75 participants, For Part 2: up to 30 participants will be enrolled in each cohort per dose level for a total of approximately 165.

Detailed description of study

The duration of the study for a participant will include:

Screening Period: up to 28 days Treatment Period: enrolled and exposed participants will receive continuous treatment until progressive disease (PD), or an occurrence of an unacceptable AE, a withdrawal of consent, or until other permanent discontinuation criteria described in the protocol are met.

The End of Treatment (EOT) visit will occur 30 days ±7 days from the last IMP administration or prior to the initiation of further therapy, whichever occurs first.

The follow-up period will occur until disease progression, the start of new anticancer therapy, death, or withdrawal of participant's consent, whichever comes first.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Solid Tumor
  • Age: 18 Years
  • Gender: Male or Female

Inclusion Criteria:

Dose escalation Part 1

  • Participants with advanced unresectable or metastatic solid tumors for which, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant Dose expansion Part 2

Cancer diagnosis:

  • Participants in Cohort A: Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
  • Participants in Cohort B: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic hepatocellular carcinoma (HCC), or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients (patients without cirrhosis must have had histological confirmation of diagnosis).
  • Participants in Cohort C: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3 gastro esophageal junction (GEJ) adenocarcinoma.
  • For participants in Cohort C: Disease with CPS scoring of <1 as determined at local laboratory with an Agency approved test (for the other cohorts: Disease with any CPS scoring. No need for CPS determination at local laboratory).
  • For participants in Cohort C: Participants must have MSI XE 'MSI' \f Abbreviation \t 'metastatic microsatellite instability' or MMR XE 'MMR' \f Abbreviation \t 'mismatch repair' status known or determined locally and must have non-MSI-H or proficient MMR (pMMR) disease to be eligible.
  • For participants in Cohort C: 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.

Measurable Disease:

        At least 1 measurable lesion per RECIST 1.1 criteria. Capable of giving signed informed
        Exclusion Criteria:
          -  Eastern Cooperative Oncology Group (ECOG XE 'ECOG' \f Abbreviation \t 'Eastern
             Cooperative Oncology Group' ) performance status of ≥2.
          -  Predicted life expectancy ≤3 months.
          -  For participants with HCC- Cohort B (Part 2): Child Pugh Class B or C liver score.
             Participants with Child Pugh Class B-7 score are allowed for Part 1.
          -  Diagnosed of any other malignancies, either progressing or requiring active
             treatments, within 2 years prior to enrollment.
          -  Known active brain metastases or leptomeningeal metastases.
          -  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 adverse events.
          -  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 potential
        participation in a clinical trial.

Updated on 14 Feb 2023 . Study ID: NCT05584670

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