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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04418661




Registration number
NCT04418661
Ethics application status
Date submitted
29/05/2020
Date registered
5/06/2020
Date last updated
1/05/2024

Titles & IDs
Public title
Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies
Scientific title
A Phase 1/2, Open-label, Multicenter, Dose Escalation and Dose Expansion Study of SAR442720 in Combination With Other Agents in Participants With Advanced Malignancies
Secondary ID [1] 0 0
U1111-1244-2555
Secondary ID [2] 0 0
TCD16210
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Neoplasm 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR442720
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Adagrasib

Experimental: SAR442720 + Pembrolizumab - Part 1:

SAR442720 (also known as RMC-4630) will be administered orally twice a week (BIW) followed by pembrolizumab which is given intravenously (IV) once every 3 weeks (Q3W). The dose of SAR442720 will be escalated or de-escalated depending on the emerging safety data of the combination.

Experimental: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score > 50% - Part 2:

SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)

Experimental: SAR442720 + Pembrolizumab: Non-small cell lung cancer with Tumor proportion score 1-49% - Part 2:

SAR442720 dose will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)

Experimental: SAR444270 + adagrasib: Dose Escalation - Part 3A; SAR442720 and adagrasib will be administered orally on a continuous basis.

Experimental: SAR444270 + adagrasib: Dose Expansion - Part 3B:

Once SAR442720 dose is confirmed in Part 3A SAR442720 and adagrasib will be administered orally on a continuous basis.

Experimental: SAR442720 + Pembrolizumab continuous - Part 4:

SAR442720 will be administered orally in combination with Pembrolizumab which is given by IV infusion once every 3 weeks (Q3W) or once every 6 weeks (Q6W)


Treatment: Drugs: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

Treatment: Drugs: Pembrolizumab
Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion

Treatment: Drugs: Adagrasib
Pharmaceutical form:Sterile Tablet Route of administration: Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events (AEs) SAR442720 and pembrolizumab
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Incidence of study-drug related Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
up to 2 years
Primary outcome [3] 0 0
Objective Response Rate (ORR)
Timepoint [3] 0 0
up to 2 years
Primary outcome [4] 0 0
Incidence of Adverse Events (AEs) SAR442720 and adagrasib
Timepoint [4] 0 0
up to 2 years
Primary outcome [5] 0 0
Part 4: Plasma concentrations of SAR442720 in combination with pembrolizumab under impact of food
Timepoint [5] 0 0
up to 2 years
Secondary outcome [1] 0 0
Part 1 and 2: Plasma concentrations of SAR442720
Timepoint [1] 0 0
up to 2 years
Secondary outcome [2] 0 0
Part 1 and 2: Serum concentration of pembrolizumab
Timepoint [2] 0 0
up to 2 years
Secondary outcome [3] 0 0
Objective response rate (ORR) Part 1 and Part 4
Timepoint [3] 0 0
up to 2 years
Secondary outcome [4] 0 0
Duration of response (DoR)
Timepoint [4] 0 0
up to 2 years
Secondary outcome [5] 0 0
Incidence of Adverse Events
Timepoint [5] 0 0
up to 2 years
Secondary outcome [6] 0 0
Time to Response (TTR)
Timepoint [6] 0 0
up to 2 years
Secondary outcome [7] 0 0
Clinical Benefit Rate (CBR)
Timepoint [7] 0 0
up to 2 years
Secondary outcome [8] 0 0
Disease Control Rate (DCR)
Timepoint [8] 0 0
up to 2 years
Secondary outcome [9] 0 0
Progression free survival (PFS)
Timepoint [9] 0 0
up to 2 years
Secondary outcome [10] 0 0
Part 3A: Plasma concentrations of SAR442720
Timepoint [10] 0 0
up to 2 years
Secondary outcome [11] 0 0
Part 3A: Plasma concentrations of adagrasib
Timepoint [11] 0 0
up to 2 years
Secondary outcome [12] 0 0
Objective Response Rate (ORR) of SAR442720 and adagrasib
Timepoint [12] 0 0
up to 2 years
Secondary outcome [13] 0 0
Duration of Response (DOR) of SAR442720 and adagrasib
Timepoint [13] 0 0
up to 2 years
Secondary outcome [14] 0 0
Part 3B: Plasma concentrations of SAR442720 and adagrasib
Timepoint [14] 0 0
up to 2 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/04/2024
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360002 - Randwick
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Woolloongabba
Recruitment hospital [3] 0 0
Investigational Site Number : 0360003 - Heidelberg West
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Argentina
State/province [3] 0 0
Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Ciudad De Buenos Aires
Country [5] 0 0
Argentina
State/province [5] 0 0
Santa Fe
Country [6] 0 0
Chile
State/province [6] 0 0
Reg Metropolitana De Santiago
Country [7] 0 0
Chile
State/province [7] 0 0
Valparaíso
Country [8] 0 0
Chile
State/province [8] 0 0
Temuco
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Chungcheongbuk-do
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Seoul-teukbyeolsi
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seongnam-si, Gyeonggi-do
Country [12] 0 0
Netherlands
State/province [12] 0 0
Leiden
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid, Comunidad De
Country [14] 0 0
Spain
State/province [14] 0 0
Valenciana, Comunidad
Country [15] 0 0
Taiwan
State/province [15] 0 0
Tainan
Country [16] 0 0
Taiwan
State/province [16] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Revolution Medicines, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Mirati Therapeutics Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04418661
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04418661