Study of SAR444881 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors

February 8, 2024 updated by: Sanofi

A Phase 1/2, Dose Escalation, Dose Expansion, and Dose Optimization Study of the Safety, Tolerability, and Anti-tumor Activity of SAR444881 Administered Alone and in Combination With Pembrolizumab, Cetuximab and/or Chemotherapy in Participants With Advanced Solid Tumors

The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization/expansion phase (Part 2). Part 1 is comprised of three sub-parts: SAR444881 administered alone (Sub-Part 1A), SAR444881 administered in combination with pembrolizumab (Sub-Part 1B), and SAR444881 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of SAR444881 per indication are administered in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed (Sub-Part 2A); and a dose expansion part where SAR444881 is administered alone (Sub-Part 2B). In Sub-Part 2A, a two-stage design will be implemented to conduct dose optimization for each indication with combination therapy- Stage 1 (Preliminary Assessment) and Stage 2 (Randomization). Study is non-randomized except Stage 2 of Sub-Part 2A which will use randomization.

Study Overview

Detailed Description

Estimated Study Duration:

Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months

Study Type

Interventional

Enrollment (Estimated)

456

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial Transparency email recommended (Toll free for US & Canada)
  • Phone Number: option 6 800-633-1610
  • Email: Contact-US@sanofi.com

Study Locations

      • Haifa, Israel, 3109601
      • Jerusalem, Israel, 91120
        • Recruiting
        • Hadassah University Medical Center
        • Contact:
      • Petah Tikva, Israel, 49100
        • Recruiting
        • Rabin Medical Center
        • Contact:
      • Ramat Gan, Israel, 52621
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Tel Aviv Sourasky Medical Center
        • Contact:
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Mitesh Borad, MD
          • Phone Number: 480-342-4800
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Contact:
          • Marwan Fakih, MD
          • Phone Number: 83087 626-256-4673
          • Email: mfakih@coh.org
    • Colorado
      • Aurora, Colorado, United States, 80045
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Zhaohui Jin, MD
          • Phone Number: 507-284-2511

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
  • Histologic confirmation of malignancy
  • Measurable disease per RECIST v1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
  • Participants must have adequate organ function as defined by laboratory tests
  • Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
  • Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma

Exclusion Criteria:

  • Active, known or suspected autoimmune disease
  • Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
  • Brain or leptomeningeal metastases
  • Known history of positive test for HIV
  • Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
  • Participants after solid organ or allogeneic hematopoietic stem cell transplant
  • History of life-threatening toxicity related to prior immune therapy
  • History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
  • Unstable or deteriorating cardiovascular disease within the previous 6 months
  • Any major surgery within 4 weeks of study drug administration
  • Prior/Concomitant Therapy:
  • Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
  • Use of other investigational drugs within 28 days
  • Prior treatment with macrophage or natural killer (NK) cells activating therapies
  • Administration of a live attenuated vaccine within 28 days

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SAR444881 Dose Escalation (Sub-Part 1A)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 will be administered intravenously (IV), every 2 weeks (Q2W).
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Names:
  • BND-22
Experimental: SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W).
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Names:
  • BND-22
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Experimental: SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C)
Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W).
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Names:
  • BND-22
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Experimental: SAR444881 Dose Optimization (Sub-Part 2A)
SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C.
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Names:
  • BND-22
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous
Experimental: SAR444881 Dose Expansion (Sub-Part 2B)
The indication for this monotherapy cohort is cholangiocarcinoma. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data.
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Names:
  • BND-22

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT)
Time Frame: Cycle 1 (28 days)
Incidence of TEAEs meeting protocol defined DLT criteria
Cycle 1 (28 days)
Part 2: Objective Response Rate (ORR) per RECIST v1.1
Time Frame: Through study completion, an average of 3 months
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Through study completion, an average of 3 months
Part 1: Incidence of treatment-emergent adverse events and serious adverse events
Time Frame: Through study completion, an average of 5 months
Through study completion, an average of 5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part 1: Maximum observed plasma concentration [Cmax]
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Part 1: Terminal elimination half-life [T1/2]
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Part 1: Area under the plasma concentration-time curve [AUC]
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Part 1: Incidence of anti-drug antibodies (ADA)
Time Frame: Through study completion, an average of 5 months
Through study completion, an average of 5 months
Part 1: Objective Response Rate (ORR) per RECIST v1.1
Time Frame: Through study completion, an average of 3 months
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Through study completion, an average of 3 months
Part 1: Serum concentration at the end of the dosing interval (Ctrough)
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Part 1: time of maximum observed serum concentration (Tmax)
Time Frame: Through study completion, an average of 2 months
Through study completion, an average of 2 months
Part 2: Duration of Response
Time Frame: Through study completion, an average of 6 months
Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first
Through study completion, an average of 6 months
Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events
Time Frame: Through study completion, an average of 6 months
Through study completion, an average of 6 months
Part 2: Cmax
Time Frame: Through study completion, an average of 3 months
Through study completion, an average of 3 months
Part 2: Ctrough
Time Frame: Through study completion, an average of 3 months
Through study completion, an average of 3 months
Part 2: Tmax
Time Frame: Through study completion, an average of 3 months
Through study completion, an average of 3 months
Part 2: T1/2
Time Frame: Through study completion, an average of 3 months
Through study completion, an average of 3 months
Part 2: AUC
Time Frame: Through study completion, an average of 3 months
Through study completion, an average of 3 months
Part 2: Incidence of ADA
Time Frame: Through study completion, an average of 6 months
Through study completion, an average of 6 months
Part 2: Progression Free Survival (PFS)
Time Frame: Up to 24 months
Time from the date of first dose of study drug to the date of first documented disease progression or death due to any cause, whichever occurs first.
Up to 24 months
PFS rate
Time Frame: At 3, 6, 9, and 12 months, and up to 24 months
Percentage of participants with PFS, per RECIST v1.1
At 3, 6, 9, and 12 months, and up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 11, 2021

Primary Completion (Estimated)

April 28, 2027

Study Completion (Estimated)

April 28, 2027

Study Registration Dates

First Submitted

January 15, 2021

First Submitted That Met QC Criteria

January 15, 2021

First Posted (Actual)

January 22, 2021

Study Record Updates

Last Update Posted (Actual)

February 12, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • TCD17465
  • BND-22-001 (Other Identifier: Biond)
  • U1111-1277-4421 (Other Identifier: WHO)
  • 2023-504937-30-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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