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Protocol No. UW19080

Principal Investigator Deming, Dustin

Phase I/II

Age Group Adult

Scope National

Sponsor Type Industry

Title A Phase 1b/2, Open-Label, Multicenter Dose-Escalation and Dose-Expansion Study of the Combination of RMC-4630 with Cobimetinib in Adult Participants with Relapsed/Refractory Solid Tumors and a Phase 1b Study of RMC-4630 with Osimertinib in Participants with Epidermal Growth Factor Receptor Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Objective The purpose of this study is to test a new drug called RMC-4630 (the study drug) in combination with cobimetinib (COTELLIC®). RMC-4630 is a new investigational (that is, experimental) drug, which means that it is not approved by the US Food and Drug Administration (FDA) or any other health authorities

Treatment This study has 3 periods:
  • Screening/Baseline period (before you begin the study to see if you qualify for the study)
  • Study Treatment period (when you will receive the study drug; this occurs in 28-day cycles)
  • Follow-up period (to check on you after your study treatment is finished)
    In addition, this study is divided into two parts:
  • Part A (dose escalation): Small group will be enrolled one at a time. Each group will receive a slightly higher dose combination of RMC-4630 or cobimetinib than the last group. These groups will be enrolled until the highest dose combination of RMC-4630 and cobimetinib with tolerated side effects is identified. Alternative dosing schedules for both study drugs may be explored. You will be assigned a dose and schedule of RMC-4630 when you start the study
  • Part B (dose expansion): Larger group will be enrolled one at a time. Each group will receive a dose level and dosing schedule already tested in Part A.

  • Description Phase 1b/2 study of RMC-4630 + Cobimetinib in Relapsed/Refract Solid Tumors with Genomic Aberrations

    Key Eligibility
  • Age 18 years or older
  • Must have advanced solid tumors that have failed, are intolerant to or are considered ineligible for standard of care anti-cancer treatments including approved drugs for oncogenic drivers in their tumor type (eg, participants with NSCLC and KRAS) mutations must have received or been offered treatment with platinum-based chemotherapy OR a PD1 or PDL1 inhibitor)
  • Must have one of the molecular aberrations and specific histotype as defined by the protocol
  • Evaluable or measurable disease per RECIST v1.1 criteria for Dose-Escalation; measurable disease (only) per RECIST v1.1 for Dose-Expansion
  • ECOG performance status of 0-1
  • Adequate hematological and organ function as defined by the protocol
  • Life expectancy of 12 weeks or greater
  • Male and female of childbearing potential must agree to adequate birth controlled as defined by the protocol
  • Can not be pregnant or breastfeeding
    EXCLUSION
  • Excluded genotypes (including co-occurring mutations) as defined by the protocol
  • Primary central nervous system (CNS) tumors
  • Known or suspected leptomeningeal or brain metastases or spinal cord compression
  • History of cerebrovascular stroke or transient ischemic attack within previous 6 months
  • ocular abnormalities are excluded: History or current retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vascular occlusion (RVO), neovascular macular degeneration, or factors considered by the investigator to present an unacceptable risk of RPED or RVO. Visible retinal pathology as assessed on ophthalmic examination that is considered a significant risk factor for RVO or RPED by an ophthalmologist
  • Cardiovascular abnormalities: Medically uncontrolled hypertension, Acute coronary syndrome (eg, unstable angina, coronary artery stenting, or angioplasty, bypass grafting) within prior 6 months, History or current uncontrolled clinically significant unstable arrhythmias,Participants who have pacemakers to control atrial arrhythmias are candidates for the study. Participants with medically controlled atrial fibrillation greater than 1 month prior to C1D1 are eligible, History of congenital long QT syndrome or prolonged QTcF interval greater than 480 ms using Fridericia's formula (unless a pacemaker is in place) or uncorrectable abnormalities in blood electrolytes (sodium, potassium, calcium, magnesium, phosphorus), Left ventricular ejection fraction (LVEF) less than institutional LLN or less than 50%, whichever is lower, Symptomatic congestive heart failure, New York Heart Association Class II or higher
  • Active, clinically significant interstitial lung disease or pneumonitis
  • Grade 2 or greater proteinuria
  • Active autoimmune disease requiring systemic treatment within past 6 months
  • HIV infection or active/chronic Hepatitis B or C
  • Impairment of gastrointestinal function
  • Patients receiving specific oncologic therapies are excluded as defined by the protocol

  • Applicable Disease Sites Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Uterus

    Status Open

    Participating Institutions UW Hospital and Clinics