Clinical trial NCT05450562: Dose Escalation and Expansion Study of SAR444200-based Regimen 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 SAR444200-based Regimen in Participants With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neoplasm
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-07-08
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1A and 1B: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: For Part 1A: from the Cycle 1, Day 1 up to Day 21For Part 1B: from Cycle 2 Day 1 up to Day 21
measure: Part 1A and 1B: Number of participants with Adverse Events (AEs)
timeFrame: the time from the first dose of study interventions up to 30 days after last dose of study interventions
measure: Part 2A: Objective Response Rate (ORR)
timeFrame: From baseline to the end of expansion study (up to 2 years)
Secondary outcomes:
measure: Part 1A and 1B: Objective Response Rate (ORR)
timeFrame: Baseline to end of dose escalation study (up to 2 years)
measure: All parts: Duration of response (DoR)
timeFrame: Baseline to end of study (up to 2 years)
measure: All parts: Assessment of PK parameters: Cmax
timeFrame: Cycle 1 Day 1 to Day 21
measure: All parts:Assessment of PK parameters: AUC0-T
timeFrame: Cycle 1 Day 1to Day 21
measure: All parts: Assessment of PK parameters: Tmax
timeFrame: Cycle 1 Day 1to Day 21
measure: All parts: Incidence of anti-drug antibodies (ADAs) to SAR444200
timeFrame: From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
measure: All parts: Incidence of anti-drug antibodies (ADAs) to atezolizumab
timeFrame: From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
measure: Part 2A: Progression Free Survival (PFS)
timeFrame: From baseline to end of expansion study (up to 2 years)
measure: Part 2A: Number of participants with Adverse Events (AEs)
timeFrame: The time from the first dose of study interventions up to 30 days after last dose of study interventions.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center- Site Number : 8400004
state: California
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai- Site Number : 8400005
state: New York
city: Providence
country: United States
facility: Lifespan Corporation- Site Number : 8400002
state: Rhode Island
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center- Site Number : 8400003
state: Texas
city: Toronto
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Quebec City
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Wuhan
country: China
facility: Investigational Site Number : 1560002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020002
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020003
city: Singapore
country: Singapore
facility: Investigational Site Number : 7020001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: