Clinical trial NCT05584670: A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-10-18
Enrollment: 291
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 291 participants will be exposed to the study intervention: approximately 75 participants in part 1, up to 210 participants in expansion/dose optimization part (part 2) and up to 6 participants in Japan cohort F.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

1. Dose escalation Part 1 and Japan Cohort F

   * 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 participants (participants 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 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.

Primary outcomes:
measure: Dose escalation and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2
timeFrame: Cycles 1 & 2 - 14 days per cycle
measure: Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
timeFrame: The time from the first dose of study interventions up to 30 days after last dose of study interventions
measure: Dose expansion/optimization: Objective response rate (ORR)
timeFrame: From baseline to the end of dose expansion/optimization (up to 2 years)
Secondary outcomes:
measure: Dose escalation and Japan Cohort F: Objective response rate (ORR)
timeFrame: From baseline to the end of dose escalation (up to 2 years)
measure: Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR)
timeFrame: From baseline to the end of study (up to 2 years)
measure: Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax
timeFrame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
measure: Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUClast
timeFrame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
measure: Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Tmax
timeFrame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
measure: Part 2b Combination: Assessment of Cetuximab serum concentration
timeFrame: Day 1 of each cycle to cycle 4 (cycle duration of 14 days)
measure: Dose escalation, expansion/optimization and Japan Cohort F: Percentage of participants with presence of anti-drug antibodies (ADAs) to SAR445877
timeFrame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)
measure: Dose expansion/optimization: Time to response
timeFrame: From baseline to end of dose expansion/optimization (up to 2 years)
measure: Dose expansion/optimization: Clinical Benefit Rate
timeFrame: From baseline to end of dose expansion/optimization (up to 2 years)
measure: Dose expansion/optimization: Progression-free survival
timeFrame: From baseline to end of dose expansion/optimization (up to 2 years)
measure: Dose expansion/optimization: Overall survival
timeFrame: From baseline to end of dose expansion/optimization (up to 2 years)
measure: Dose expansion/optimization: Number of participants with Adverse events (AE)
timeFrame: The time from the first dose of study interventions up to 30 days after last dose of study interventions.
Other outcomes:
Locations:
city: Fairway
country: United States
facility: University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008
state: Kansas
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute- Site Number : 8400006
state: Michigan
city: Hackensack
country: United States
facility: John Theurer Cancer Center Site Number : 8400001
state: New Jersey
city: Providence
country: United States
facility: Rhode Island Hospital Site Number : 8400004
state: Rhode Island
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center Site Number : 8400005
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center - 825 Eastlake Ave E- Site Number : 8400010
state: Washington
city: Be'er Ya'akov
country: Israel
facility: Investigational Site Number : 3760004
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS_Investigational Site Number : 3760005
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS_Investigational Site Number : 3760003
city: Tel-Aviv
country: Israel
facility: Investigational Site Number : 3760001
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis_Investigational Site Number : 5280001
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC_Investigational Site Number : 5280003
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON_Investigational Site Number : 7240007
city: Madrid
country: Spain
facility: START MADRID_Hospital Universitario HM Sanchinarro - CIOCC_Investigational Site Number : 7240005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: