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

Sanofi

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neoplasm

Treatments: Biological: Atezolizumab; Biological: SAR444200

Study type: Interventional

Funder types: Industry

Identifiers

NCT05450562

2021-006623-17 (EudraCT Number)

U1111-1264-3207 (Registry Identifier)

TCD17240

Details and patient eligibility

About

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.

Full 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.

Enrollment: 106 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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106 participants in 3 patient groups

SAR444200 - Dose Escalation Phase (Part 1A)

Experimental group

Description:

SAR444200 will be administered as intravenous injection as monotherapy in participants with GPC3+ solid tumors over a 21-day cycle

Treatment:

Biological: SAR444200

SAR444200 - Dose Expansion Phase (Part 2A)

Experimental group

Description:

SAR444200 will be administered as intravenous injection in participants with GPC3+ NSCLC over a 21-day cycle

Treatment:

Biological: SAR444200

SAR444200 and Atezolizumab combination therapy - Dose Escalation Phase (Part 1B)

Experimental group

Description:

SAR444200 in combination with atezolizumab will be administered as intravenous injection in participants with GPC3+ solid tumors over a 21-day cycle

Treatment:

Biological: SAR444200

Biological: Atezolizumab