Clinical trial NCT03634982: Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
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
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-08-17
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

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: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: up to 3 years
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: 28 days
Secondary outcomes:
measure: Cmax
timeFrame: up to 3 years
measure: Tmax
timeFrame: up to 3 years
measure: Area Under the Curve (AUC)
timeFrame: up to 3 years
measure: t1/2
timeFrame: up to 3 years
measure: Accumulation Ratio
timeFrame: up to 3 years
measure: Overall Response Rate (ORR)
timeFrame: up to 3 years
measure: Duration of Response (DOR)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Orange
country: United States
facility: UC Irvine - Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UC San Francisco - Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute - Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffit Cancer Center
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Oklahoma City
country: United States
facility: University of Oklahoma - Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology, PLLC
state: Tennessee
city: Austin
country: United States
facility: University of Texas at Austin - Dell Medical School
state: Texas
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc.
role: STUDY_DIRECTOR
References: