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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: Part 1- SAR442720 140 mg BIW + Pembrolizumab - Participants were administered SAR442720 140 milligram (mg) orally twice a week (BIW) on Days 1 and 4 along with pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day cycles until disease progression, unacceptable adverse events (AEs), or the participant's or investigator's decision to stop the treatment.

Experimental: Part 1- SAR442720 200mg BIW + Pembrolizumab - Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 along with pembrolizumab 200 mg via IV infusion Q3W in 21-day cycles until disease progression, unacceptable AEs, or the participant's or investigator's decision to stop the treatment.

Experimental: Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%) - Participants with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS)\>=50% non-small cell lung cancer (NSCLC) were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg once in every 6 weeks (Q6W) (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

Experimental: Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%) - Participants with PDL1 TPS 1% - 49% NSCLC were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg Q6W (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

Experimental: Part 3A- SAR442720 100mg BIW + Adagrasib - Participants were administered SAR442720 100 mg orally BIW on Days 1 and 2 along with adagrasib 400 mg orally twice daily (BID) in 21-day cycles until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

Experimental: Part 4- SAR442720 200mg + Pembrolizumab - Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles (as tablet during the first cycle and as capsule from Cycle 2) along with an IV infusion of pembrolizumab 200 mg Q3W (21-day cycle)or 400 mg Q6W (42-day cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.


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
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
From first dose of IMP up to 30 days after the last dose; approximately 27 weeks
Primary outcome [2] 0 0
Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Cycle 1 (21 days)
Primary outcome [3] 0 0
Part 2: Percentage of Participants With Objective Response Rate (ORR)
Timepoint [3] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Primary outcome [4] 0 0
Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
Timepoint [4] 0 0
From first dose of IMP up to 30 days after the last dose; approximately 7 weeks
Primary outcome [5] 0 0
Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab
Timepoint [5] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on C1 D1, C1 D15, C2 D1; Pre-dose on C1 D8 and C6 D1; end of treatment (Week 45)
Primary outcome [6] 0 0
Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules
Timepoint [6] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2D1
Primary outcome [7] 0 0
Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules
Timepoint [7] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1
Primary outcome [8] 0 0
Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules
Timepoint [8] 0 0
Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1
Secondary outcome [1] 0 0
Part 1: Plasma Concentration of SAR442720
Timepoint [1] 0 0
Pre-dose, 2, 8, hours post-dose on C1 D1 and C2D1; pre-dose C1D8, C1D15, and C6D1; 2 hours C2D2; and end of treatment (Week 22)
Secondary outcome [2] 0 0
Part 2: Plasma Concentration of SAR442720
Timepoint [2] 0 0
Pre-dose and 2 hours post-dose C1D1 and C2D1; pre-dose on C1D8, C1D15, C6D1; and end of treatment (Week 104)
Secondary outcome [3] 0 0
Parts 1 and 2: Serum Concentration of Pembrolizumab
Timepoint [3] 0 0
Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1
Secondary outcome [4] 0 0
Parts 1 and 4: Percentage of Participants With Objective Response Rate
Timepoint [4] 0 0
Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks (Part 1), 46 weeks (Part 4)
Secondary outcome [5] 0 0
Part 1: Duration of Response (DoR)
Timepoint [5] 0 0
Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks
Secondary outcome [6] 0 0
Part 2: Duration of Response
Timepoint [6] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Secondary outcome [7] 0 0
Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
Timepoint [7] 0 0
From first dose of IMP up to 30 days after the last dose; approximately 111 weeks
Secondary outcome [8] 0 0
Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events
Timepoint [8] 0 0
From first dose of IMP up to 30 days after the last dose; approximately 50 weeks
Secondary outcome [9] 0 0
Part 2: Time to Response (TTR)
Timepoint [9] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Secondary outcome [10] 0 0
Part 2: Percentage of Participants With Clinical Benefit Rate
Timepoint [10] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Secondary outcome [11] 0 0
Part 2: Percentage of Participants With Disease Control Rate
Timepoint [11] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Secondary outcome [12] 0 0
Part 2: Progression Free Survival (PFS)
Timepoint [12] 0 0
Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks
Secondary outcome [13] 0 0
Part 3A: Plasma Concentration of SAR442720
Timepoint [13] 0 0
Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post-dose C1D1; pre-dose C1D8; pre-dose, 0.5, 1, 2, 4, 6 post-dose C1D15, and end of treatment (Week 3)
Secondary outcome [14] 0 0
Part 3A: Plasma Concentration of Adagrasib
Timepoint [14] 0 0
Pre-dose, 1, 2, 4, 6, 8 post-dose C1D1 and C1D15; pre-dose C1D8
Secondary outcome [15] 0 0
Part 3A: Percentage of Participants With Objective Response Rate
Timepoint [15] 0 0
Tumor assessments performed till end of treatment, approximately 3 weeks
Secondary outcome [16] 0 0
Part 3A: Duration of Response
Timepoint [16] 0 0
Tumor assessments performed till end of treatment, approximately 3 weeks

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 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.

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 - Sydney
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Woolloongabba
Recruitment hospital [3] 0 0
Investigational Site Number : 0360003 - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3084 - Melbourne
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
Ciudad De Buenos Aires
Country [4] 0 0
Argentina
State/province [4] 0 0
Santa Fe
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
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
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid, Comunidad De
Country [13] 0 0
Spain
State/province [13] 0 0
Valenciana, Comunidad
Country [14] 0 0
Taiwan
State/province [14] 0 0
Tainan City
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taipei City

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


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04418661