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Trial record 1 of 1 for:    TCD17620
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A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT05584670
Recruitment Status : Recruiting
First Posted : October 18, 2022
Last Update Posted : May 9, 2024
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE October 7, 2022
First Posted Date  ICMJE October 18, 2022
Last Update Posted Date May 9, 2024
Actual Study Start Date  ICMJE November 29, 2022
Estimated Primary Completion Date January 19, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2022)
  • Dose escalation: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2 [ Time Frame: Cycles 1 & 2 - 14 day per cycle ]
    DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)
  • Dose escalation: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) [ Time Frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions ]
    Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
  • Dose expansion: Objective response rate (ORR) [ Time Frame: From baseline to the end of dose expansion (up to 2 years) ]
    Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2022)
  • Dose escalation Objective response rate (ORR) [ Time Frame: From baseline to the end of dose escalation (up to 2 years) ]
    Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Dose escalation & expansion Duration of response (DoR) [ Time Frame: From baseline to the end of study (up to 2 years) ]
    DoR is defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) determined by Investigator per RECIST 1.1 or death from any cause, whichever occurs first
  • Dose escalation & expansion Assessment of SAR445877 Cmax [ Time Frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) ]
    Maximum plasma concentration observed
  • Dose escalation & expansion Assessment of SAR445877 AUC0-T [ Time Frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) ]
    Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)
  • Dose escalation & expansion Incidence of anti-drug antibodies (ADAs) to SAR445877 [ Time Frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days) ]
    Incidence of patients with anti-drug antibodies (ADAs) to SAR445877
  • Time to response is defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of confirmed PR or CR determined by Investigator per RECIST 1.1 [ Time Frame: From baseline to end of dose expansion (up to 2 years) ]
    Time to response is defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of confirmed PR or CR determined by Investigator per RECIST 1.1
  • 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 1.1 [ Time Frame: From baseline to end of dose expansion (up to 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 1.1
  • PFS is 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 1.1 or death from any cause, whichever occurs first [ Time Frame: From baseline to end of dose expansion (up to 2 years) ]
    PFS is 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 1.1 or death from any cause, whichever occurs first
  • Number of participants with Adverse events (AE) [ Time Frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions. ]
    Presence of adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 or American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors
Official Title  ICMJE A Phase 1/2, 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 in Adults With Advanced Solid Tumors
Brief Summary

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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: SAR445877
Concentrate for solution for infusion
Study Arms  ICMJE
  • Experimental: SAR445877 Escalation Phase (Part 1)
    SAR445877 monotherapy will be administered intravenously in patients with solid tumors over a 14-day cycle.
    Intervention: Drug: SAR445877
  • Experimental: SAR445877 Expansion Phase: Cohort A (Part 2)
    SAR445877 monotherapy will be administered intravenously (IV) in patients with non-small cell lung cancer (NSCLC).
    Intervention: Drug: SAR445877
  • Experimental: SAR445877 Expansion Phase: Cohort B (Part 2)
    SAR445877 monotherapy will be administered intravenously in patients with hepatocellular carcinoma (HCC).
    Intervention: Drug: SAR445877
  • Experimental: SAR445877 Expansion Phase: Cohort C (Part 2)
    Participants will receive SAR445877 monotherapy will be administered IV in patients with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ).
    Intervention: Drug: SAR445877
  • Experimental: SAR445877 Expansion Phase: Cohort D (Part 2)
    Participants will receive SAR445877 monotherapy will be administered IV in patients with immune infiltrated tumor type.
    Intervention: Drug: SAR445877
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 13, 2022)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 15, 2028
Estimated Primary Completion Date January 19, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (metastatic microsatellite instability) or MMR (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 consent.

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.

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free for US & Canada) 800-633-1610 ext option 6 contact-us@sanofi.com
Listed Location Countries  ICMJE Israel,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05584670
Other Study ID Numbers  ICMJE TCD17620
U1111-1277-4827 ( Registry Identifier: ICTRP )
2022-001239-95 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Current Responsible Party Sanofi
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sanofi
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP