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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04717375
• Other study ID #: TCD17465
• Secondary ID: BND-22-001U1111-
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 11, 2021
• Est. completion date: February 24, 2027

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 456
• Est. completion date: February 24, 2027
• Est. primary completion date: February 24, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Neoplasm

Intervention

Drug:
• SAR444881
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Pembrolizumab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Cetuximab
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
• Carboplatin
Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous
• Pemetrexed
Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous

Locations

Country	Name	City	State
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Medical Center	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Yale Cancer Center	New Haven	Connecticut
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT)	Incidence of TEAEs meeting protocol defined DLT criteria	Cycle 1 (28 days)
Primary	Part 1: Incidence of treatment-emergent adverse events and serious adverse events		Through study completion, an average of 5 months
Primary	Part 2: Objective Response Rate (ORR) per RECIST v1.1	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
Secondary	Part 1: Objective Response Rate (ORR) per RECIST v1.1	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
Secondary	Part 1: Maximum observed plasma concentration [Cmax]		Through study completion, an average of 2 months
Secondary	Part 1: Serum concentration at the end of the dosing interval (Ctrough)		Through study completion, an average of 2 months
Secondary	Part 1: time of maximum observed serum concentration (Tmax)		Through study completion, an average of 2 months
Secondary	Part 1: Terminal elimination half-life [T1/2]		Through study completion, an average of 2 months
Secondary	Part 1: Area under the plasma concentration-time curve [AUC]		Through study completion, an average of 2 months
Secondary	Part 1: Incidence of anti-drug antibodies (ADA)		Through study completion, an average of 5 months
Secondary	Part 2: Progression Free Survival (PFS)	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
Secondary	PFS rate	Percentage of participants with PFS, per RECIST v1.1	At 3, 6, 9, and 12 months, and up to 24 months
Secondary	Part 2: Duration of Response	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
Secondary	Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events		Through study completion, an average of 6 months
Secondary	Part 2: Cmax		Through study completion, an average of 3 months
Secondary	Part 2: Ctrough		Through study completion, an average of 3 months
Secondary	Part 2: Tmax		Through study completion, an average of 3 months
Secondary	Part 2: T1/2		Through study completion, an average of 3 months
Secondary	Part 2: AUC		Through study completion, an average of 3 months
Secondary	Part 2: Incidence of ADA		Through study completion, an average of 6 months