Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04418661
Recruitment Status : Recruiting
First Posted : June 5, 2020
Last Update Posted : July 6, 2022
Sponsor:
Collaborators:
Revolution Medicines, Inc.
Mirati Therapeutics Inc.
Information provided by (Responsible Party):
Sanofi

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.

Condition or disease Intervention/treatment Phase
Metastatic Neoplasm Drug: SAR442720 Drug: Pembrolizumab Drug: Adagrasib Phase 1 Phase 2

Detailed Description:

This open label Phase 1 multicenter study is designed to evaluate the safety and maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SAR442720 in combination with pembrolizumab in participants with solid tumors in Part 1.

In Part 2, in the expansion cohort (Cohort A) we will assess the antitumor activity and safety of SAR442720 combined with pembrolizumab in participants with metastatic 1L lung cancer.

In Part 3, we will evaluate the safety, MTD, RP2D and antitumor activity of SAR442720 in combination with adagrasib in participants with lung cancer and KRAS G12C mutation.

In Part 4, we will evaluate the impact of the formulations (formulation 1 and formulation 2) and of the food on the PK of SAR442720 when dosed in combination with pembrolizumab. The expected duration of study intervention for participants may vary, based on progression date; median expected duration of study per participant is estimated to be about 10 months in Part 1, Part 3 and Part 4 (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for long term follow-up) and in Part 2 16 months (up to 1 month for screening, a median of 12 months for treatment and a median of 3 months for long term follow up.)

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 133 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 9, 2020
Estimated Primary Completion Date : July 15, 2025
Estimated Study Completion Date : July 15, 2025

Arm Intervention/treatment
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.

Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

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

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)

Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

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

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)

Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

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

Experimental: SAR444270 + adagrasib: Dose Escalation
Part 3A; SAR442720 and adagrasib will be administered orally on a continuous basis.
Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

Drug: Adagrasib
Pharmaceutical form:Sterile Tablet Route of administration: Oral

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.

Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

Drug: Adagrasib
Pharmaceutical form:Sterile Tablet Route of administration: Oral

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)

Drug: SAR442720
Pharmaceutical form: Varies Route of administration: Varies

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




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) SAR442720 and pembrolizumab [ Time Frame: 21 days ]

    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.


  2. Incidence of study-drug related Dose Limiting Toxicities (DLTs) [ Time Frame: up to 2 years ]

    Part 1 and 3A:

    Incidence of study drug-related dose-limiting toxicities (DLTs) in Cycle 1.


  3. Objective Response Rate (ORR) [ Time Frame: up to 2 years ]

    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


  4. Incidence of Adverse Events (AEs) SAR442720 and adagrasib [ Time Frame: up to 2 years ]

    Part 3A:

    Incidence, nature, and severity of TEAEs and SAEs, graded according to NCI CTCAEv5.0 for the combination of SAR442720 and adagrasib.


  5. Part 4: Plasma concentrations of SAR442720 in combination with pembrolizumab under impact of food [ Time Frame: up to 2 years ]

Secondary Outcome Measures :
  1. Part 1 and 2: Plasma concentrations of SAR442720 [ Time Frame: up to 2 years ]
  2. Part 1 and 2: Serum concentration of pembrolizumab [ Time Frame: up to 2 years ]
  3. Objective response rate (ORR) Part 1 and Part 4 [ Time Frame: up to 2 years ]

    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.


  4. Duration of response (DoR) [ Time Frame: up to 2 years ]

    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.


  5. Incidence of Adverse Events [ Time Frame: up to 2 years ]

    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.


  6. Time to Response (TTR) [ Time Frame: up to 2 years ]

    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).


  7. Clinical Benefit Rate (CBR) [ Time Frame: up to 2 years ]

    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.


  8. Disease Control Rate (DCR) [ Time Frame: up to 2 years ]

    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.


  9. Progression free survival (PFS) [ Time Frame: up to 2 years ]

    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.


  10. Part 3A: Plasma concentrations of SAR442720 [ Time Frame: up to 2 years ]
  11. Part 3A: Plasma concentrations of adagrasib [ Time Frame: up to 2 years ]
  12. Objective Response Rate (ORR) of SAR442720 and adagrasib [ Time Frame: up to 2 years ]

    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.


  13. Duration of Response (DOR) of SAR442720 and adagrasib [ Time Frame: up to 2 years ]

    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.


  14. Part 3B: Plasma concentrations of SAR442720 and adagrasib [ Time Frame: up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (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.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04418661


Contacts
Layout table for location contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 Ext. option 6 Contact-US@sanofi.com

Locations
Show Show 20 study locations
Sponsors and Collaborators
Sanofi
Revolution Medicines, Inc.
Mirati Therapeutics Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04418661    
Other Study ID Numbers: TCD16210
U1111-1244-2555 ( Registry Identifier: ICTRP )
2020-000436-22 ( EudraCT Number )
First Posted: June 5, 2020    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: July 5, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Pembrolizumab
Adagrasib
Antineoplastic Agents, Immunological
Antineoplastic Agents