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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04418661
Ethics application status
Date submitted
29/05/2020
Date registered
5/06/2020
Date last updated
29/03/2021

Titles & IDs
Public title
Safety Study of SAR442720 in Combination With Pembrolizumab in Patients With Advanced Malignancies
Scientific title
A Phase 1, Open-label, Multicenter, Safety Study of SAR442720 in Combination With Pembrolizumab in Patients 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

Experimental: SAR442720 - SAR442720 (also known as RMC-4630) will be administered orally with pembrolizumab which is given by 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.


Treatment: Drugs: SAR442720
Pharmaceutical form:Capsule Route of administration: Oral

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of study-drug related Dose Limiting Toxicities (DLTs) - Incidence and nature of DLTs assessed as the occurrence of adverse events (AE) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Incidence of Adverse Events - Incidence, nature, and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the NCI CTCAE v5 for the combination of SAR442720 and pembrolizumab.
Timepoint [2] 0 0
up to 2 years
Secondary outcome [1] 0 0
PK of SAR442720 - Plasma concentrations of SAR442720.
Timepoint [1] 0 0
up to 2 years
Secondary outcome [2] 0 0
PK of pembrolizumab - Serum concentrations of pembrolizumab.
Timepoint [2] 0 0
up to 2 years
Secondary outcome [3] 0 0
Objective response rate (ORR) - Percentage of participants with a best response of complete response (CR) or partial response (PR) of SAR442720 and pembrolizumab based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Timepoint [3] 0 0
up to 2 years
Secondary outcome [4] 0 0
Duration of response (DoR) - Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.
Timepoint [4] 0 0
up to 2 years

Eligibility
Key inclusion criteria
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: KRAS
mutations and amplifications, BRAF Class 3 mutations, or NF1 LOF mutations

- 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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Predicted life expectancy <3 months.

- Primary central nervous system (CNS) tumors.

- Symptomatic or impending cord compression.

- 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 of planned treatment start

- 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
N/A
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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
Recruitment hospital [1] 0 0
Investigational Site Number 0360003 - Heidelberg West
Recruitment hospital [2] 0 0
Investigational Site Number 0360002 - Randwick
Recruitment hospital [3] 0 0
Investigational Site Number 0360001 - Woolloongabba
Recruitment postcode(s) [1] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
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
Korea, Republic of
State/province [3] 0 0
Seoul
Country [4] 0 0
Spain
State/province [4] 0 0
Madrid / Madrid
Country [5] 0 0
Taiwan
State/province [5] 0 0
Tainan
Country [6] 0 0
Taiwan
State/province [6] 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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

- To characterize the safety and tolerability of SAR442720 in combination with
pembrolizumab in patients with advanced solid tumors including NSCLC who progressed on
anti-PD-1/PD L1 containing therapy and advanced colorectal cancer (CRC) after
progression to all standard of care (SOC) therapy.

- To define the MTD and RP2D for the combination of SAR442720 and pembrolizumab in
patients with solid tumors

Secondary Objective:

- To document the pharmacokinetic (PK) of SAR442720 in combination with pembrolizumab and
to document the PK of pembrolizumab in combination with SAR442720

- To estimate the anti-tumor effects of SAR442720 in combination with pembrolizumab in all
participants
Trial website
https://clinicaltrials.gov/show/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
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

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