A Phase I/II, Open Label, First-in-human, Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR445877 Administered as Monotherapy or in Combination With Other Anticancer Therapies in Adults With Advanced Solid Tumors

Study Identifier:
TCD17620
CT.gov Identifier:
NCT05584670
EudraCT Identifier:
202200123995
EU Trial (CTIS) Number:
2023-507141-28-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

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 therapeutic dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW) and in combination with other anticancer therapies when applicable.

A multicohort dose expansion/dose optimization Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy and in combination with cetuximab: 2 recommended doses for expansion/optimization of SAR445877 identified from dose escalation part 1 will be tested in different indications in monotherapy and in combination with other anticancer therapies as applicable.

Approximately 291 participants will be exposed to the study intervention: approximately 75 participants in part 1, up to 210 participants in expansion/dose optimization part (part 2) and up to 6 participants in Japan cohort F.

To evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activities of SAR445877 administered intravenously as a single agent in adult participants with advanced unresectable or metastatic solid tumors

The study is conducted in 2 parts. The Part 1 (dose escalation) will determine the maximum tolerated dose or maximum administered dose per occurrence of dose limiting toxicities in the first 28-days (cycle 1 and 2), recommended dose(s), and the overall safety and tolerability profile of SAR445877. A multicohort Part 2 (dose expansion) would assess the safety and preliminary efficacy of SAR445877 (2 dose levels in at least 1 indication, as applicable) and will include cohorts with advanced solid tumors regardless of the tumor proportion score/combined positive score and cohort with a negative expression of the PDL1.

Adverse effects will be assessed per National Cancer Institute, Common Terminology Criteria for Adverse Events version 5.0 and American Society for Transplantation and Cellular Therapy consensus grading. Tumor response will be determined according to Response Evaluation Criteria in Solid Tumors criteria.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Melanoma
Renal
Gastric
Liver
Solid Tumor
Mesothelioma
Digestive & Intestinal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: SAR445877 Escalation Phase (Part 1A)
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Drug: Experimental: SAR445877 Escalation Phase (Part1B)
Drug: Drug: ADG126
Drug: Experimental: SAR445877 Escalation Phase (Part 1C)
Drug: Drug: Bevacizumab
Drug: Other Names:
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A)
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A)
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A)
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A)
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A)
Drug: Experimental: SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2B)
Drug: Experimental: SAR445877 Expansion/optimization Phase: Cohort E2 (Part 2A)
Drug: Experimental: SAR445877 Expansion/optimization Phase: Cohort E3 (Part 2B)
Drug: Drug: Cetuximab
Drug: Experimental: SAR445877 Expansion/Optimization Phase Cohort G1 (Part 2C)
Drug: Experimental: SAR445877 Expansion/Optimization Phase Cohort G2 (Part 2C)
Drug: Experimental: SAR445877 Expansion/Optimization Phase Cohort G3 (Part 2C)
Drug: 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.
Drug: The duration of the study for a participant will include:
Drug: 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.
Drug: 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.
Drug: 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.
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Inclusion Criteria: 1. Dose escalation Part 1A and Japan Cohort F:
  • - Patients with advanced unresectable or metastatic solid tumors for whom standard alternative therapies are unavailable or not in the best interests of the patient, as determined by the principal investigator (or co-investigator).
  • 2. Dose escalation Part 1B: Patients with advanced unresectable or metastatic melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), colorectal cancer (CRC) (high microsatellite instability [MSI-H]/mismatch repair deficiency [dMMR]), malignant pleural mesothelioma, or esophageal squamous cell carcinoma (ESCC), for whom standard alternative therapies are unavailable or not in the best interests of the patient, as determined by the principal investigator (or co-investigator).
  • 3. Dose expansion/optimization Part 2:
  • Cancer diagnosis:
  • - Subjects in Cohorts A1 and A2 (Part 2A): Confirmed diagnosis of metastatic NSCLC by histological or cytological examination.
  • - Subjects in Cohort B (Part 2A): Patients with a confirmed diagnosis of advanced unresectable or metastatic HCC by histological or cytological examination, or patients with cirrhosis clinically diagnosed with HCC based on American Association for the Liver and Disease (AASLD) criteria (if cirrhosis is absent, the diagnosis must be confirmed by histological examination).
  • - Subjects in Cohorts C1 and C2 (Part 2A): Patients
  • with a confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC), or Siewert type 2 and 3 esophagogastric junction (GEJ) adenocarcinoma by histological or cytological examination.
  • - Composite Positive Score (CPS) score is not required. It is not necessary to measure CPS in the laboratory of the participating medical institution.
  • - Patients with tumors that have a known or determined metastatic microsatellite instability (MSI) or mismatch repair (MMR) status, and are not MSI-H or have normal mismatch repair (pMMR) are considered eligible.
  • - For patients whose human epidermal growth factor receptor 2 (HER2)/neu status is unknown, the HER2/neu status must be determined at the participating medical institution. Patients with HER2/neu-negative status are eligible. Patients with HER2/neu-positive tumors are considered eligible if there is a record of progression observed during treatment, including previously approved HER2-targeted therapies.
  • - Subjects in Part 2A cohorts E1 and E2, Part 2B cohort E3, and Part 2D cohorts H1 and H2: Patients who have been definitively diagnosed with advanced, unresectable, or metastatic CRC by histological or cytological examination.
  • - Subjects with MSI status in Part 2A cohorts E1 and E2, and Part 2B cohort E3: Patients with known or determined MSI status at the participating medical institution and who have tumors that are not MSI-H are considered eligible.
  • - Subjects in Part 2A cohorts E1 and E2, Part 2B cohort E3, and Part 2D cohorts H1 and H2: Patients with RAS mutations and BRAF mutations in CRC are eligible for enrollment.
  • - Subjects in Part 2C cohorts G1, G2, and G3: Patients with a confirmed diagnosis of unresectable locally advanced or metastatic melanoma by histological examination.
  • 4. Previous cancer treatment history (dose escalation/optimization Part 2 only):
  • - Subjects in cohorts A1 and A2: Patients with a history of treatment with one or more systemic therapies for metastatic disease who are not candidates for available standard of care (SOC).
  • - Subjects in cohort B: Patients with a history of one or more cancer therapies, including regimens containing anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) antibodies, who have progressed after developing primary or secondary resistance to anti-PD1/PD -L1 antibodies.
  • - Subjects in cohorts C1 and C2: Patients who have progressed or relapsed after receiving one or more lines of treatment with or without anti-PD1/PD-L1 antibodies, depending on the SOC of each country.
  • - Subjects in cohort D: Patients with a history of treatment with one or more systemic therapies for advanced/metastatic disease who are not candidates for available SOC.
  • - Part 2A cohorts E1 and E2 and Part 2D cohorts H1 and H2 must have been unresponsive to or experienced relapse after prior treatment with two or more regimens.
  • - Cohort E3 must have been unresponsive to or experienced relapse after prior treatment with one or more regimens. Patients who received cetuximab or other anti-epidermal growth factor receptor (EGFR) therapy as part of prior treatment are eligible.
  • - Part 2C cohorts G1, G2 and G3: Patients who have received one or more lines of prior treatment for advanced/metastatic melanoma and/or who have no SOC treatment options, have refused SOC treatment, or are intolerant to SOC treatment. Measurable lesions: -
  • Patients
  • with one or more measurable lesions based on the Criteria for Evaluation of Treatment Response in Solid Tumors (RECIST) 1.1 criteria.
  • Part 2D: Patients with adequate coagulation function. Patients receiving anticoagulant therapy (excluding platelet anticoagulants) must confirm that their International Normalized Ratio (INR) is within the appropriate therapeutic range. Patients must be able to provide a signed informed consent form.
Exclusion criteria
  • Eastern Cooperative Oncology Group (ECOG) 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.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Melanoma
Renal
Gastric
Liver
Solid Tumor
Mesothelioma
Digestive & Intestinal