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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04717375
Recruitment Status : Recruiting
First Posted : January 22, 2021
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Neoplasm Drug: SAR444881 Drug: Pembrolizumab Drug: Cetuximab Drug: Carboplatin Drug: Pemetrexed Phase 1 Phase 2

Detailed Description:

Estimated Study Duration:

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 456 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 11, 2021
Estimated Primary Completion Date : May 14, 2027
Estimated Study Completion Date : May 14, 2027
Arms and Interventions
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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).
 Drug: SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Name: 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).
 Drug: SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Name: BND-22

Drug: Pembrolizumab
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).
 Drug: SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Name: BND-22

Drug: Cetuximab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Experimental: SAR444881 Dose Optimization (Sub-Part 2A)
SAR444881 Dose Optimization in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), 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.
 Drug: SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Name: BND-22

Drug: Pembrolizumab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous

Drug: Carboplatin
Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous

Drug: Pemetrexed
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 will be either relapsed or refractory NSCLC, head and neck squamous cell carcinoma (HNSCC), cholangiocarcinoma, or GC/GEJ. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data.
 Drug: SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Other Name: BND-22


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Part 1: Incidence of treatment-emergent adverse events and serious adverse events [ Time Frame: Through study completion, an average of 5 months ]
  3. 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


Secondary Outcome Measures :
  1. 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

  2. Part 1: Maximum observed plasma concentration [Cmax] [ Time Frame: Through study completion, an average of 2 months ]
  3. Part 1: Serum concentration at the end of the dosing interval (Ctrough) [ Time Frame: Through study completion, an average of 2 months ]
  4. Part 1: time of maximum observed serum concentration (Tmax) [ Time Frame: Through study completion, an average of 2 months ]
  5. Part 1: Terminal elimination half-life [T1/2] [ Time Frame: Through study completion, an average of 2 months ]
  6. Part 1: Area under the plasma concentration-time curve [AUC] [ Time Frame: Through study completion, an average of 2 months ]
  7. Part 1: Incidence of anti-drug antibodies (ADA) [ Time Frame: Through study completion, an average of 5 months ]
  8. Part 2: Progression Free Survival [ Time Frame: Through study completion, an average of 3 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

  9. 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

  10. Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events [ Time Frame: Through study completion, an average of 6 months ]
  11. Part 2: Cmax [ Time Frame: Through study completion, an average of 3 months ]
  12. Part 2: Ctrough [ Time Frame: Through study completion, an average of 3 months ]
  13. Part 2: Tmax [ Time Frame: Through study completion, an average of 3 months ]
  14. Part 2: T1/2 [ Time Frame: Through study completion, an average of 3 months ]
  15. Part 2: AUC [ Time Frame: Through study completion, an average of 3 months ]
  16. Part 2: Incidence of ADA [ Time Frame: Through study completion, an average of 6 months ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04717375


Contacts
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Contact: Trial Transparency email recommended (Toll free for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Mitesh Borad, MD    480-342-4800      
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Marwan Fakih, MD    626-256-4673 ext 83087    mfakih@coh.org   
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Christopher Lieu, MD    720-848-3532    CHRISTOPHER.LIEU@CUANSCHUTZ.EDU   
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Ingrid Palma    203-200-2486    Ingrid.palma@yale.edu   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Zhaohui Jin, MD    507-284-2511      
Israel
Rambam Health Care Campus Recruiting
Haifa, Israel, 3109601
Contact: Liat Rapaport    972-4-777-6731    L_Rapaport@rambam.health.gov.il   
Hadassah University Medical Center Recruiting
Jerusalem, Israel, 91120
Contact: Cecilia Lellouche    972-2-6779129    CECILIAL@hadassah.org.il   
Rabin Medical Center Recruiting
Petah Tikva, Israel, 49100
Contact: Gal Medalia    972-3-937-8023    Galmed@clalit.org.il   
Sheba Medical Center Recruiting
Ramat Gan, Israel, 52621
Contact: Ilanit Redinsky    972-3-530-4498    Ilanit.Redinsky@sheba.health.gov.il   
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 6423906
Contact: Limor Ben Zvi    972-3-697-3193    limorb@tlvmc.gov.il   
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04717375    
Other Study ID Numbers: TCD17465
BND-22-001 ( Other Identifier: Biond )
U1111-1277-4421 ( Other Identifier: WHO )
First Posted: January 22, 2021    Key Record Dates
Last Update Posted: September 21, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carboplatin
Pembrolizumab
Pemetrexed
Cetuximab
Antineoplastic Agents
Antineoplastic Agents, Immunological
 Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors