A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

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 or in Combination With Other Anticancer Therapies in Adults With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05584670
• Other study ID #: TCD17620
• Secondary ID: U1111-1277-48272
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 29, 2022
• Est. completion date: September 27, 2028

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

This is a Phase 1/2, open label, multiple cohort study to assess the safety and preliminary efficacy of SAR445877 as a monotherapy or in combination with other anticancer therapies for participants aged at least 18 years with advanced unresectable or metastatic solid tumors.

The study will include 2 parts:

A dose escalation Part 1: for finding the therapeutic dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW) and in combination with other anticancer therapies when applicable.

A multicohort dose expansion/dose optimization Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy and in combination with cetuximab: 2 recommended doses for expansion/optimization of SAR445877 identified from dose escalation part 1 will be tested in different indications in monotherapy and in combination with other anticancer therapies as applicable.

Approximately 285 participants will be enrolled to the study intervention: approximately 75 participants in part 1 and up to 210 participants in expansion/dose optimization part (part 2).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 285
• Est. completion date: September 27, 2028
• Est. primary completion date: January 19, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. Dose expansion/optimization Part 2

Cancer diagnosis:

• Participants in Cohorts A1 and A2: 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 Cohorts C1 and C2: 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 Cohorts C1 and C2: 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 Cohorts C1 and C2: 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 Cohorts C1 and C2: 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

Participants in Cohorts E1, E2 and E3

• Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic colorectal cancer

• Participants must have MSI status known or determined locally and must have non-MSI-H disease to be eligible.

• Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment.

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• SAR445877
Concentrate for solution for infusion
• Cetuximab
Solution for infusion

Locations

Country	Name	City	State
Israel	Hadassah Medical Center - PPDS_Investigational Site Number : 3760005	Jerusalem
Israel	Sheba Medical Center - PPDS_Investigational Site Number : 3760003	Ramat Gan
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis_Investigational Site Number : 5280001	Amsterdam	Noord-Holland
Netherlands	Erasmus MC_Investigational Site Number : 5280003	Rotterdam
Spain	Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON_Investigational Site Number : 7240007	Barcelona
Spain	START MADRID_Hospital Universitario HM Sanchinarro - CIOCC_Investigational Site Number : 7240005	Madrid
United States	University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008	Fairway	Kansas
United States	John Theurer Cancer Center Site Number : 8400001	Hackensack	New Jersey
United States	University of Texas MD Anderson Cancer Center Site Number : 8400005	Houston	Texas
United States	Rhode Island Hospital Site Number : 8400004	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Israel,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose escalation: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2	DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)	Cycles 1 & 2 - 14 days per cycle
Primary	Dose escalation: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)	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	The time from the first dose of study interventions up to 30 days after last dose of study interventions
Primary	Dose expansion/optimization: Objective response rate (ORR)	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	From baseline to the end of dose expansion/optimization (up to 2 years)
Secondary	Dose escalation: Objective response rate (ORR)	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	From baseline to the end of dose escalation (up to 2 years)
Secondary	Dose escalation & expansion/optimization: Duration of response (DoR)	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	From baseline to the end of study (up to 2 years)
Secondary	Dose escalation & expansion/optimization: Assessment of SAR445877 Cmax	Maximum plasma concentration observed	Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Secondary	Dose escalation & expansion/optimization: Assessment of SAR445877 AUC0-T	Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)	Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Secondary	Dose escalation & expansion/optimization: Assessment of SAR445877 Tmax	First time to reach Cmax	Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Secondary	Dose escalation & expansion/optimization: Assessment of Cetuximab serum concentration	Pre-dose concentration	Day 1 of each cycle to cycle 4 (cycle duration of 14 days)
Secondary	Dose escalation & expansion/optimization: Incidence of anti-drug antibodies (ADAs) to SAR445877	Proportion of participants with anti-drug antibodies (ADAs) to SAR445877	From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)
Secondary	Dose expansion/optimization: Time to response	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	From baseline to end of dose expansion/optimization (up to 2 years)
Secondary	Dose expansion/optimization: Clinical Benefit Rate	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	From baseline to end of dose expansion/optimization (up to 2 years)
Secondary	Dose expansion/optimization: Progression-free survival	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	From baseline to end of dose expansion/optimization (up to 2 years)
Secondary	Dose expansion/optimization: Number of participants with Adverse events (AE)	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	The time from the first dose of study interventions up to 30 days after last dose of study interventions.