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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/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
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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
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Secondary ID [1]
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U1111-1244-2555
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Secondary ID [2]
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TCD16210
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Metastatic Neoplasm
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence of Adverse Events (AEs) SAR442720 and pembrolizumab
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Assessment method [1]
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Part 1:
Incidence, nature, and severity of treatment emergent AEs and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for the combination of SAR442720 and pembrolizumab.
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Timepoint [1]
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21 days
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Primary outcome [2]
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Incidence of study-drug related Dose Limiting Toxicities (DLTs)
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Assessment method [2]
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Part 1 and 3A:
Incidence of study drug-related dose-limiting toxicities (DLTs) in Cycle 1.
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Timepoint [2]
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up to 2 years
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Primary outcome [3]
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Objective Response Rate (ORR)
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Assessment method [3]
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Part 2 and 3B:
Objective response rate defined as the proportion of participants who have a confirmed CR or partial response (PR) determined by investigator, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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Timepoint [3]
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up to 2 years
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Primary outcome [4]
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Incidence of Adverse Events (AEs) SAR442720 and adagrasib
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Assessment method [4]
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Part 3A:
Incidence, nature, and severity of TEAEs and SAEs, graded according to NCI CTCAEv5.0 for the combination of SAR442720 and adagrasib.
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Timepoint [4]
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up to 2 years
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Primary outcome [5]
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Part 4: Plasma concentrations of SAR442720 in combination with pembrolizumab under impact of food
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Assessment method [5]
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Timepoint [5]
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up to 2 years
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Secondary outcome [1]
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Part 1 and 2: Plasma concentrations of SAR442720
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Assessment method [1]
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Timepoint [1]
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up to 2 years
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Secondary outcome [2]
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Part 1 and 2: Serum concentration of pembrolizumab
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Assessment method [2]
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Timepoint [2]
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up to 2 years
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Secondary outcome [3]
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Objective response rate (ORR) Part 1 and Part 4
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Assessment method [3]
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Part 1 and Part 4:
Objective response rate of SAR442720 and pembrolizumab in all participants. ORR of combination therapy with SAR442720 and pembrolizumab will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.
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Timepoint [3]
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up to 2 years
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Secondary outcome [4]
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Duration of response (DoR)
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Assessment method [4]
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Part 1 and Part 2 and 3B:
Duration of response per RECIST v1.1 is defined as the interval from the first documentation of CR (complete response) or PR (partial response) to the earlier of the first documentation of definitive disease progression or death due to any cause, whichever occurs first.
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Timepoint [4]
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up to 2 years
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Secondary outcome [5]
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Incidence of Adverse Events
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Assessment method [5]
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Part 2 and 3B and Part 4:
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.
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Timepoint [5]
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up to 2 years
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Secondary outcome [6]
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Time to Response (TTR)
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Assessment method [6]
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Part 2 and 3B:
Time to response (TTR) defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of PR or CR determined by the Investigator per RECIST v1.1 (for NSCLC).
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Timepoint [6]
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up to 2 years
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Secondary outcome [7]
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Clinical Benefit Rate (CBR)
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Assessment method [7]
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Part 2 and 3B:
Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months (determined by the Investigator per RECIST v1.1.
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Timepoint [7]
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up to 2 years
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Secondary outcome [8]
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Disease Control Rate (DCR)
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Assessment method [8]
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Part 2 and 3B:
Disease control rate (DCR) including confirmed CR or PR or stable disease (SD) as determined by the Investigator per RECIST v1.1.
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Timepoint [8]
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up to 2 years
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Secondary outcome [9]
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Progression free survival (PFS)
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Assessment method [9]
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Part 2 and 3B:
Progression free survival (PFS), defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by the Investigator as per RECIST v1.1 or death due to any cause, whichever occurs first.
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Timepoint [9]
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up to 2 years
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Secondary outcome [10]
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Part 3A: Plasma concentrations of SAR442720
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Assessment method [10]
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Timepoint [10]
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up to 2 years
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Secondary outcome [11]
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Part 3A: Plasma concentrations of adagrasib
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Assessment method [11]
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Timepoint [11]
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up to 2 years
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Secondary outcome [12]
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Objective Response Rate (ORR) of SAR442720 and adagrasib
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Assessment method [12]
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Part 3A:
ORR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.
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Timepoint [12]
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up to 2 years
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Secondary outcome [13]
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Duration of Response (DOR) of SAR442720 and adagrasib
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Assessment method [13]
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Part 3:
DOR of SAR442720 and adagrasib in all participants. ORR of combination therapy with SAR442720 and adagrasib will be based on RECIST v1.1.
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Timepoint [13]
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up to 2 years
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Secondary outcome [14]
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Part 3B: Plasma concentrations of SAR442720 and adagrasib
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Assessment method [14]
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Timepoint [14]
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up to 2 years
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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.
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Minimum age
18
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/06/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
4/04/2024
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Sample size
Target
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Accrual to date
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Final
65
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
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Recruitment hospital [1]
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Investigational Site Number : 0360002 - Randwick
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Recruitment hospital [2]
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Investigational Site Number : 0360001 - Woolloongabba
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Recruitment hospital [3]
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Investigational Site Number : 0360003 - Heidelberg West
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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4102 - Woolloongabba
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Recruitment postcode(s) [3]
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3081 - Heidelberg West
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Texas
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Country [3]
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Argentina
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State/province [3]
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Buenos Aires
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Country [4]
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Argentina
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State/province [4]
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Ciudad De Buenos Aires
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Country [5]
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Argentina
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State/province [5]
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Santa Fe
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Country [6]
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Chile
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State/province [6]
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Reg Metropolitana De Santiago
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Country [7]
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Chile
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State/province [7]
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Valparaíso
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Country [8]
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Chile
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State/province [8]
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Temuco
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Country [9]
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Korea, Republic of
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State/province [9]
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Chungcheongbuk-do
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Country [10]
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Korea, Republic of
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State/province [10]
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Seoul-teukbyeolsi
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Country [11]
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Korea, Republic of
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State/province [11]
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Seongnam-si, Gyeonggi-do
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Country [12]
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Netherlands
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State/province [12]
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Leiden
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Country [13]
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Spain
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State/province [13]
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Madrid, Comunidad De
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Country [14]
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Spain
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State/province [14]
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Valenciana, Comunidad
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Country [15]
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Taiwan
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State/province [15]
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Tainan
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Country [16]
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Taiwan
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State/province [16]
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Taipei
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Sanofi
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Revolution Medicines, Inc.
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Address [1]
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Country [1]
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Other collaborator category [2]
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Commercial sector/Industry
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Name [2]
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Mirati Therapeutics Inc.
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Address [2]
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Country [2]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04418661
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Sciences & Operations
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Address
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Sanofi
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04418661
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