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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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.