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

NCT03634982 | Unknown Phase 1 FDA Drug

• 1 other identifier: RMC-4630-01
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 12

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).

Conditions

Solid Tumors

Keywords

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; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events (AEs)

  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

  up to 3 years

• Number of participants with dose limiting toxicities (DLTs)

  Incidence and nature of DLTs with RMC-4630 monotherapy

  28 days

Secondary Outcomes (7)

• Cmax

  up to 3 years

• Tmax

  up to 3 years

• Area Under the Curve (AUC)

  up to 3 years

• t1/2

  up to 3 years

• Accumulation Ratio

  up to 3 years

Study Arms (1)

RMC-4630

EXPERIMENTAL

RMC-4630 for oral administration

Drug: RMC-4630

Interventions

RMC-4630 DRUG

RMC-4630 for oral administration

RMC-4630

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Revolution Medicines, Inc.: lead
• Sanofi: collaborator

Study Sites (12)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UC Irvine - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UC San Francisco - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Sarah Cannon Research Institute - Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Oklahoma - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

University of Texas at Austin - Dell Medical School

Austin, Texas, 78712, United States

Location

MeSH Terms

Conditions

Noonan Syndrome; Melanoma; Skin Neoplasms; Ovarian Neoplasms; Uterine Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; 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; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Uterine Cervical Diseases; Carcinoma; Bronchial Diseases

Study Officials

• Revolution Medicines, Inc.

  Revolution Medicines, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 17, 2018
• Study Start: September 28, 2018
• Primary Completion: March 31, 2023
• Study Completion: May 31, 2023
• Last Updated: September 1, 2022

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)