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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 : November 14, 2018
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Revolution Medicines, Inc.

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
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


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




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. pERK [ Time Frame: up to 3 years ]
    On-treatment versus baseline comparison of pharmacodynamic markers of RMC-4630 (e.g., pERK [phosphorylated form of extracellular signal-regulated kinase]) on peripheral blood mononuclear cells or newly obtained tumor samples by immunoassays or immunohistochemistry (IHC)

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

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



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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: RTK mutations, amplifications or rearrangements, KRASG12, BRAF Class 3, or NF1 LOF 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

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

Locations
United States, California
UC Irvine Medical Center - 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         
United States, Florida
Sarah Cannon Research Institute - Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Terri Peterson    941-377-9993      
Principal Investigator: Judy Wang, MD         
United States, Oklahoma
University of Oklahoma - Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Study Coordinator    405-271-8778 ext option 2      
Principal Investigator: Susanna Ulahannan, MD         
United States, Tennessee
Sarah Cannon Research Institute - Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: ASKSARAH    877-691-7274    ASKSARAH@scresearch.net   
Principal Investigator: Howard Burris, III, MD         
Sponsors and Collaborators
Revolution Medicines, Inc.
Sanofi
Investigators
Study Director: Revolution Medicines, Inc. Revolution Medicines, Inc.

Responsible Party: Revolution Medicines, Inc.
ClinicalTrials.gov Identifier: NCT03634982     History of Changes
Other Study ID Numbers: RMC-4630-01
First Posted: August 17, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
RTK
KRAS G12
BRAF Class 3
NF1 LOF
advanced solid tumor
advanced solid malignancies
melanoma
skin cancer
ovarian cancer
pancreatic 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