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Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT03634982
Recruitment Status : Recruiting
First Posted : August 17, 2018
Last Update Posted : October 19, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.

Study Description
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Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: RMC-4630 Phase 1

Detailed Description:
This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: RMC-4630
RMC-4630 for oral administration
 Drug: RMC-4630
RMC-4630 for oral administration


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) [ Time Frame: up to 3 years ]
    Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy

  2. Number of participants with dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
    Incidence and nature of DLTs with RMC-4630 monotherapy


Secondary Outcome Measures :
  1. Cmax [ Time Frame: up to 3 years ]
    Peak plasma concentration of RMC-4630

  2. Tmax [ Time Frame: up to 3 years ]
    Time to achieve peak plasma concentration of RMC-4630

  3. Area Under the Curve (AUC) [ Time Frame: up to 3 years ]
    Area under the plasma concentration time curve of RMC-4630

  4. t1/2 [ Time Frame: up to 3 years ]
    Elimination half-life of RMC-4630

  5. Accumulation Ratio [ Time Frame: up to 3 years ]
    Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosing

  6. Overall Response Rate (ORR) [ Time Frame: up to 3 years ]
    Overall response rate of RMC-4630 per RECIST v1.1

  7. Duration of Response (DOR) [ Time Frame: up to 3 years ]
    Duration of response of RMC-4630 per RECIST v1.1


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant (male or female) ≥18 years of age
  • Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
  • Adequate hematologic, hepatic and renal function
  • Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
  • Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria

Exclusion Criteria:

  • Known or suspected leptomeningeal or brain metastases or spinal cord compression
  • Primary central nervous system (CNS) tumors
  • Clinically significant cardiac disease
  • Active, clinically significant interstitial lung disease or pneumonitis
  • History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
  • Known HIV infection
  • Active/chronic hepatitis B or C infection
  • Any other 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 prior/concomitant therapy
  • Females who are pregnant or breastfeeding
Contacts and Locations
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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): NCT03634982


Contacts
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Contact: Revolution Medicines, Inc. (650) 779-2300 CT-Inquiries@RevMed.com

Locations
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United States, Arizona
Honor Health Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer    480-323-1791    joschaffer@honorhealth.com   
Principal Investigator: Michael Gordon, MD         
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Marianna Koczywas, MD    626-256-4673 ext 83793    MKoczywas@coh.org   
Principal Investigator: Marianna Koczywas, MD         
UC Irvine - Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Sai-Hong Ignatius Ou, MD, PhD    877-824-3627    ucstudy@uci.edu   
Principal Investigator: Sai-Hong Ignatius Ou, MD, PhD         
UC Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Steffany Lim, CCRP    916-734-0561    sllim@ucdavis.edu   
Principal Investigator: Jonathan Riess, MD         
UC San Francisco - Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Delaire Fattah    415-514-9286    delaire.fattah@ucsf.edu   
Principal Investigator: Caroline McCoach, MD         
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Tara Wells    720-848-0755    TARA.WELLS@CUANSCHUTZ.EDU   
Principal Investigator: Jose Pacheco, MD         
United States, Florida
Sarah Cannon Research Institute - Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Terri Peterson    941-377-9993    tpeterson@flcancer.com   
Principal Investigator: Judy Wang, MD         
Moffit Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Germaine M González-Vazquez    813-745-6636    germaine.gonzalezvazquez@moffitt.org   
Principal Investigator: Eric Haura, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Bryan Marion    617-632-3383    bryan_marion@dfci.harvard.edu   
Contact: Kaitlin Morton    617-582-8013    kaitlin_morton@dfci.harvard.edu   
Principal Investigator: Pasi Janne, MD, PhD         
United States, Oklahoma
University of Oklahoma - Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Dena Suthers    405-271-8778 ext option 2    SCC-Clinical-Trials-Office@ouhsc.edu   
Principal Investigator: Susanna Ulahannan, MD         
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Dee McComb    615-329-7478    researchreferrals@scresearch.net   
Principal Investigator: Howard Burris, III, MD         
United States, Texas
University of Texas at Austin - Dell Medical School Recruiting
Austin, Texas, United States, 78712
Contact: Anna Capasso    512-495-5516    anna.capasso@austin.utexas.edu   
Principal Investigator: Anna Capasso, MD         
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
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Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.
More Information
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Responsible Party: Revolution Medicines, Inc.
ClinicalTrials.gov Identifier: NCT03634982    
Other Study ID Numbers: RMC-4630-01
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Revolution Medicines, Inc.:
SHP2
PTPN11
NSCLC
EGFR
KRAS G12
BRAF Class 3
NF1 LOF
advanced solid tumor
advanced solid malignancies
melanoma
skin cancer
ovarian cancer
endometrium/uterus cancer
bladder cancer
cervical cancer
 Carcinoma, Non-Small-Cell Lung
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Esophageal Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Glandular and Epithelial
Gastrointestinal Neoplasms
Additional relevant MeSH terms:
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Neoplasms