Safety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies
Study of Investigational Medication in Combination with Other Agents for Advanced Cancers
Study Overview
Primary Objectives:
- Part 1
- To characterize the safety and tolerability of SAR442720 in combination with pembrolizumab in participants with advanced solid tumors.
- To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in participants with solid tumors.
- Part 2
- To determine the anti-tumor activity of SAR442720 in combination with pembrolizumab.
- Part 3A
- To define the MTD and RP2D for the combination of SAR442720 and adagrasib in participants with KRAS G12C NSCLC
- To characterize the safety and tolerability of SAR442720 in combination with adagrasib in participants with KRAS G12C NSCLC
- Part 3B
- To determine the anti-tumor activity of SAR442720 in combination with adagrasib in participants with KRAS G12C NSCLC
- Part 4
- To evaluate the impact of food on the PK of SAR442720 when dosed with pembrolizumab.
- To evaluate the impact of the formulations (formulation 1 and formulation 2) on the PK of SAR442720 when dosed with pembrolizumab.
Secondary Objectives:
- Part 1
- To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with SAR442720.
- To estimate the anti-tumor effects of SAR442720 with pembrolizumab.
- Part 2
- To assess the safety profile of SAR442720 combined with pembrolizumab.
- To assess other indicators of anti-tumor activity.
- To assess the PK of SAR442720 with pembrolizumab, and the PK of pembrolizumab with SAR442720.
- Part 3A
- To characterize the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720.
- To estimate the anti-tumor effects of SAR442720 with adagrasib
- Part 3B
- To assess the safety profile of SAR442720 with adagrasib in participants with KRAS G12C NSCLC.
- To assess other indicators of anti-tumor activity.
- To assess the PK of SAR442720 with adagrasib, and the PK of adagrasib with SAR442720.
- Part 4
- To assess the safety and tolerability of SAR442720 formulations with pembrolizumab
- To estimate the anti-tumor effects of SAR442720 with pembrolizumab.
Study Details
This open label Phase 1 multicenter study was designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SAR442720 in combination with pembrolizumab in participants with solid tumors in Part 1.
In Part 2, in the expansion cohort (Cohort A) we assessed the antitumor activity and safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung cancer.
In Part 3, we evaluated the safety, MTD, RP2D and antitumor activity of SAR442720 in combination with adagrasib in participants with lung cancer and KRAS G12C mutation.
In Part 4, we evaluated the impact of the formulations (formulation 1 and formulation 2) and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. The expected duration of study intervention for participants may vary, based on progression date; median expected duration of study per participant was estimated to be about 10 months in Part 1, Part 3 and Part 4 (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for long term follow-up) and in Part 2 16 months (up to 1 month for screening, a median of 12 months for treatment and a median of 3 months for long term follow up.)
Eligibility Criteria
You may be eligible for this study if you meet the following criteria:
- Conditions: Metastatic Neoplasm
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Age: 18 years or above
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Gender: All
Inclusion Criteria:
- Participants must be ≥ 18 years of age.
- Histologically proven diagnosis of advanced solid tumors.
- Participants must have one or more of the following molecular aberrations (Part 1): KRAS mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations.
- Participants must have following molecular aberration (Part 3A and 3B): - KRAS G12C mutation.
- At least 1 measurable disease per RECIST 1.1 criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Woman of childbearing potential must agree to follow contraceptive guidance.
- Capable of giving signed informed consent.
Exclusion Criteria:
- Predicted life expectancy <3 months.
- Primary central nervous system (CNS) tumors.
- Symptomatic or impending cord compression. Stable CNS disease was allowed.
- History of cerebrovascular stroke or transient ischemic attack within previous 6 months.
- Prior solid organ or hematologic transplant.
- History or current retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vascular occlusion (RVO), neovascular macular degeneration.
- Any clinically significant cardiac disease.
- Active, known or suspected autoimmune disease.
- History of or current interstitial lung disease or pneumonitis.
- Receipt of a live-virus vaccination within 28 days, viral vaccine that do not contain live virus within 7 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
- Known infection with human immunodeficiency virus (HIV), known uncontrolled hepatitis B infection, active tuberculosis, or severe infection requiring parenteral antibiotic treatment.
- Inadequate hematologic, hepatic and renal function.
- Known second malignancy.
- Impairment of gastrointestinal function.
- Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol.
- History of severe allergic reaction to any of the study intervention components.
The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
This study investigates the safety and effectiveness of an investigational medication in combination with other agents for treating advanced cancers. The study involves different parts focusing on various combinations: Part 1 and 2 test the investigational medication with pembrolizumab in participants with solid tumors and metastatic lung cancer, respectively. Part 3 examines the combination with adagrasib in participants with a specific lung cancer mutation called KRAS G12C. Part 4 evaluates how food and different formulations affect the medication when used with pembrolizumab.
Participants will undergo procedures that include taking the investigational medication in combination with either pembrolizumab or adagrasib, depending on their cancer type and study part. Pembrolizumab and adagrasib are other medications used to treat cancer. The study also involves regular health assessments to monitor safety and effectiveness, and to understand how the body processes the investigational medication. Participants will be closely observed for any side effects or changes in their health status.
- Who can participate: Participants must be 18 years or older with advanced solid tumors and specific genetic mutations, such as KRAS G12C for Part 3.
- Study details: Participants will receive SAR442720 with other agents, such as pembrolizumab or adagrasib, and undergo regular assessments to monitor treatment safety and effectiveness.
