Clinical Trials /

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

NCT03634982

Description:

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).

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

    <li>Brief Title: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumorsli><li>Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumorsli>

Clinical Trial IDs

    <li>ORG STUDY ID: RMC-4630-01li><li>NCT ID: NCT03634982li>

Conditions

    <li>Solid Tumorsli>

Interventions

<td>RMC-4630td><td/><td>RMC-4630td>
DrugSynonymsArms

Purpose

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).

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.
    

Trial Arms

<td>RMC-4630td><td>Experimentaltd><td>RMC-4630 for oral administrationtd><td>
    <li>RMC-4630li>
td>
NameTypeDescriptionInterventions

Eligibility 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
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>Number of participants with adverse events (AEs)td><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>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 monotherapytd>

Secondary Outcome Measures

<td>Measure:td><td>Cmaxtd><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Peak plasma concentration of RMC-4630td>
<td>Measure:td><td>Tmaxtd><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Time to achieve peak plasma concentration of RMC-4630td>
<td>Measure:td><td>Area Under the Curve (AUC)td><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Area under the plasma concentration time curve of RMC-4630td>
<td>Measure:td><td>t1/2td><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Elimination half-life of RMC-4630td>
<td>Measure:td><td>Accumulation Ratiotd><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Ratio of accumulation of RMC-4630 from a single dose to steady state with repeated dosingtd>
<td>Measure:td><td>pERKtd><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>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)td>
<td>Measure:td><td>Overall Response Rate (ORR)td><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Overall response rate of RMC-4630 per RECIST v1.1td>
<td>Measure:td><td>Duration of Response (DOR)td><td>Time Frame:td><td>up to 3 yearstd><td>Safety Issue:td><td/><td>Description:td><td>Duration of response of RMC-4630 per RECIST v1.1td>

Details

<td>Phase:td><td>Phase 1td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Not yet recruitingtd><td>Lead Sponsor:td><td>RevolutionMedicines, Inc.td>

Trial Keywords

    <li>SHP2li><li>PTPN11li><li>NSCLCli><li>EGFRli><li>RTKli><li>KRAS G12li><li>BRAF Class 3li><li>NF1 LOFli><li>advanced solid tumorli><li>advanced solid malignanciesli><li>melanomali><li>skin cancerli><li>ovarian cancerli><li>pancreatic cancerli><li>endometrium/uterus cancerli><li>bladder cancerli><li>cervical cancerli><li>Carcinoma, Non-Small-Cell Lungli><li>Neoplasms, Squamous Cellli><li>Carcinoma, Squamous Cellli><li>Esophageal Neoplasmsli><li>Carcinoma, Bronchogenicli><li>Bronchial Neoplasmsli><li>Lung Neoplasmsli><li>Respiratory Tract Neoplasmsli><li>Thoracic Neoplasmsli><li>Neoplasms by Siteli><li>Neoplasmsli><li>Lung Diseasesli><li>Respiratory Tract Diseasesli><li>Neoplasms, Glandular and Epithelialli><li>Gastrointestinal Neoplasmsli><li>Digestive System Neoplasmsli><li>Head and Neck Neoplasmsli><li>Digestive System Diseasesli><li>Esophageal Diseasesli><li>Gastrointestinal Diseasesli>

Last Updated

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