Neoplasm
Conditions
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.
Interventions
BIOLOGICALSAR444200
Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion
BIOLOGICALAtezolizumab
concentrate for solution for infusion Route of administration: intravenous (IV) infusion
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1A and 1B: Number of participants with Dose Limiting Toxicities (DLTs) | For Part 1A: from the Cycle 1, Day 1 up to Day 21For Part 1B: from Cycle 2 Day 1 up to Day 21 | Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) |
| Part 1A and 1B: Number of participants with Adverse Events (AEs) | the time from the first dose of study interventions up to 30 days after last dose of study interventions | 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 |
| Part 2A: Objective Response Rate (ORR) | From baseline to the end of expansion study (up to 2 years) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All parts:Assessment of PK parameters: AUC0-T | Cycle 1 Day 1to Day 21 | Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T) |
| All parts: Assessment of PK parameters: Tmax | Cycle 1 Day 1to Day 21 | Time to reach Cmax |
| All parts: Incidence of anti-drug antibodies (ADAs) to SAR444200 | From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days | Incidence of participants with anti-drug antibodies to SAR444200 |
| Part 1A and 1B: Objective Response Rate (ORR) | Baseline to end of dose escalation study (up to 2 years) | 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) |
| Part 2A: Progression Free Survival (PFS) | From baseline to end of expansion study (up to 2 years) | 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) |
| Part 2A: Number of participants with Adverse Events (AEs) | The time from the first dose of study interventions up to 30 days after last dose of study interventions. | 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 |
| 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 | — |
| All parts: Duration of response (DoR) | Baseline to end of study (up to 2 years) | 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) |
| All parts: Assessment of PK parameters: Cmax | Cycle 1 Day 1 to Day 21 | Maximum plasma concentration observed |
Countries
Canada, China, Singapore, South Korea, United States
Outcome results
None listed