- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04717375
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
Status
Recruiting
Intervention / Treatment
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
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-
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Haifa, Israel, 3109601
- Recruiting
- Rambam Health Care Campus
-
Contact:
- Liat Rapaport
- Phone Number: 972-4-777-6731
- Email: L_Rapaport@rambam.health.gov.il
-
Jerusalem, Israel, 91120
- Recruiting
- Hadassah University Medical Center
-
Contact:
- Cecilia Lellouche
- Phone Number: 972-2-6779129
- Email: CECILIAL@hadassah.org.il
-
Petah Tikva, Israel, 49100
- Recruiting
- Rabin Medical Center
-
Contact:
- Gal Medalia
- Phone Number: 972-3-937-8023
- Email: Galmed@clalit.org.il
-
Ramat Gan, Israel, 52621
- Recruiting
- Sheba Medical Center
-
Contact:
- Ilanit Redinsky
- Phone Number: 972-3-530-4498
- Email: Ilanit.Redinsky@sheba.health.gov.il
-
Tel Aviv, Israel, 6423906
- Recruiting
- Tel Aviv Sourasky Medical Center
-
Contact:
- Limor Ben Zvi
- Phone Number: 972-3-697-3193
- Email: limorb@tlvmc.gov.il
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-
-
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Arizona
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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
- Recruiting
- University of Colorado Cancer Center
-
Contact:
- Christopher Lieu, MD
- Phone Number: 720-848-3532
- Email: CHRISTOPHER.LIEU@CUANSCHUTZ.EDU
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Recruiting
- Yale Cancer Center
-
Contact:
- Ingrid Palma
- Phone Number: 203-200-2486
- Email: Ingrid.palma@yale.edu
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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:
|
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:
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:
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:
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:
|
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
Additional Relevant MeSH Terms
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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