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.
This open label Phase 1 multicenter study is 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 will assess the antitumor activity and
safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung
cancer.
In Part 3, we will evaluate 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 will evaluate 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 is 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.)
Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies
Drug: Pembrolizumab
Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion
Drug: Adagrasib
Pharmaceutical form:Sterile Tablet Route of administration: Oral
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 is 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 is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
University of California Irvine Medical Center-Site Number:8400002
Orange, California, United States
~University of Texas - MD Anderson Cancer Center-Site Number:8400001
Houston, Texas, United States
Investigational Site Number :0320001
Caba, Buenos Aires, Argentina
Investigational Site Number :0320004
Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number :0320003
Rosario, Santa Fe, Argentina
Investigational Site Number :0320002
Buenos Aires, Argentina
Investigational Site Number :0360002
Randwick, New South Wales, Australia
Investigational Site Number :0360001
Woolloongabba, Queensland, Australia
Investigational Site Number :0360003
Heidelberg West, Victoria, Australia
Investigational Site Number :1520004
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520001
Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number :1520003
Viña del Mar, Valparaíso, Chile
Investigational Site Number :1520002
Temuco, Chile
Investigational Site Number :4100003
Cheongju-si, Chungcheongbuk-do, Korea, Republic of
Investigational Site Number :4100001
Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number :4100002
Seongnam-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number :5280001
Leiden, Netherlands
Investigational Site Number :7020001
Singapore, Singapore
Investigational Site Number :7240001
Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number :7240002
Madrid / Madrid, Madrid, Comunidad De, Spain
Investigational Site Number :7240003
Valencia / Valencia, Valenciana, Comunidad, Spain
Investigational Site Number :1580002
Tainan, Taiwan
Investigational Site Number :1580001
Taipei, Taiwan
Clinical Sciences & Operations, Study Director
Sanofi