Dose Escalation and Expansion Study of SAR444200-based Regimen in Adult Participants With Advanced Solid Tumors

Neoplasm 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 SAR444200-based Regimen in Participants With Advanced Solid Tumors.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05450562
• Other study ID #: TCD17240
• Secondary ID: U1111-1264-32072
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 20, 2022
• Est. completion date: December 12, 2030

Study information

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

Clinical Trial Summary

This is Phase 1/Phase 2, open label, multiple cohort, first-in-human study to evaluate safety, PK, PDy and efficacy of SAR444200 as a monotherapy or in combination with other anti-cancer agents for participants aged at least 18 years with previously treated metastatic malignancies.

Description:

Treatment Period: enrolled participants will receive continuous treatment until disease progression (PD), unacceptable adverse event (AE), or other permanent discontinuation criteria.

The End of Treatment visit will occur 30 days ±7 days from last IMP administration or prior to initiation of further therapy, whichever occurs first.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: December 12, 2030
• Est. primary completion date: December 12, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cancer diagnosis for participants for Part 1A and Part 1B:

1. Metastatic and/or unresectable HCC diagnosed by histology and/or cytology, or diagnosed clinically by the American Association for the Study of Liver Diseases (AASLD) criteria for participants with liver cirrhosis (participants without liver cirrhosis must be diagnosed histologically) OR Other histology/cytology proven advanced and/or metastatic non-HCC solid tumors

2. Not amenable to available standard of care: participants must have experienced disease progression on/after standard of care, or no acceptable standard curative or palliative treatments exist (or are no longer effective), according to Investigator judgement, or the participant declines standard of care therapy.

• Cancer diagnosis for participants for Part 2A:

1. Metastatic NSCLC with no actionable driver gene mutants (such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)), diagnosed by histology and/or cytology not amenable to available standard of care and must have progressed on/after therapy that included an anti-PD(L)-1 agent with or without platinum-based chemotherapy.

2. Progressive disease should be observed during the course of anti-PD(L)-1 therapy or within 12 weeks from the last dose of anti-PD(L)-1 therapy

• Additional for Part 2A: At least 1 measurable lesion per RECIST 1.1 criteria

• For all participants:

1. Positive GPC3 expression on tumor tissue as determined locally or centrally

2. 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: Child Pugh Class B or C liver score within 14 days of initiation of IMP. Participants with Child Pugh Class B-7 score are allowed for Part 1A.

• Known active brain metastases or leptomeningeal metastases.

• History of allogenic or solid organ transplant

• 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

• Significant cardiovascular disease within 3 months prior to initiation of IMP, uncontrolled arrhythmia requiring medication, or unstable angina.

• Ongoing AEs caused by any prior anti-cancer therapy >Grade 2

• Known uncontrolled human immunodeficiency virus (HIV), hepatitis B infection, or known untreated current hepatitis C infection

• Known second malignancy either progressing or requiring active treatment within the last year.

• For combination therapy: Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events

• Receipt of a live-virus vaccination within 28 days of planned treatment start.

• For Part 2A, has received prior GPC3 targeted anticancer treatment.

• Current pneumonitis or interstitial lung disease, or history of interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Neoplasm

Intervention

Biological:
• SAR444200
Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion
• Atezolizumab
concentrate for solution for infusion Route of administration: intravenous (IV) infusion

Locations

Country	Name	City	State
Canada	Investigational Site Number : 1240001	Quebec
Canada	Investigational Site Number : 1240002	Toronto	Ontario
China	Investigational Site Number : 1560001	Shanghai
China	Investigational Site Number : 1560002	Wuhan
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Singapore	Investigational Site Number : 7020001	Singapore
Singapore	Investigational Site Number : 7020002	Singapore
Singapore	Investigational Site Number : 7020003	Singapore
United States	~MD Anderson Cancer Center Site Number : 8400003	Houston	Texas
United States	USCA Norris Comprehensive Cancer Center Site Number : 8400004	Los Angeles	California
United States	Mount Sinai Hospital Site Number : 8400005	New York	New York
United States	Lifespan Site Number : 8400002	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  China,  Korea, Republic of,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1A and 1B: Number of participants with Dose Limiting Toxicities (DLTs)	Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	For Part 1A: from the Cycle 1, Day 1 up to Day 21For Part 1B: from Cycle 2 Day 1 up to Day 21
Primary	Part 1A and 1B: Number of participants with Adverse Events (AEs)	Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	the time from the first dose of study interventions up to 30 days after last dose of study interventions
Primary	Part 2A: Objective Response Rate (ORR)	ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	From baseline to the end of expansion study (up to 2 years)
Secondary	Part 1A and 1B: Objective Response Rate (ORR)	ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Baseline to end of dose escalation study (up to 2 years)
Secondary	All parts: Duration of response (DoR)	DoR defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) or death from any cause, whichever occurs first determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Baseline to end of study (up to 2 years)
Secondary	All parts: Assessment of PK parameters: Cmax	Maximum plasma concentration observed	Cycle 1 Day 1 to Day 21
Secondary	All parts:Assessment of PK parameters: AUC0-T	Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)	Cycle 1 Day 1to Day 21
Secondary	All parts: Assessment of PK parameters: Tmax	Time to reach Cmax	Cycle 1 Day 1to Day 21
Secondary	All parts: Incidence of anti-drug antibodies (ADAs) to SAR444200	Incidence of participants with anti-drug antibodies to SAR444200	From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
Secondary	All parts: Incidence of anti-drug antibodies (ADAs) to atezolizumab		From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
Secondary	Part 2A: Progression Free Survival (PFS)	PFS, defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 (or death due to any cause, whichever occurs first)	From baseline to end of expansion study (up to 2 years)
Secondary	Part 2A: Number of participants with Adverse Events (AEs)	Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0	The time from the first dose of study interventions up to 30 days after last dose of study interventions.