Clinical trial NCT05462717: Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
Official title: Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Pancreatic Ductal Adenocarcinoma
Advanced Solid Tumor
Keywords: RMC-6291
RAS(ON)
KRAS
KRASG12C
KRASG12C(ON)
Targeted therapy
Metastatic cancer
Lung Cancer
Lung Neoplasms
Thoracic Neoplasms
Non-small Cell Lung Cancer
Carcinoma, Non-Small Cell Lung
NSCLC
Colorectal Cancer
Colonic Neoplasms
CRC
Appendiceal Cancer
KRAS mutation
STK11/LKB1
KEAP1
bronchial neoplasms
respiratory tract neoplasms
neoplasms by site
neoplasms
Colon Cancer
Rectal Cancer
lung disease
respiratory tract diseases
Pancreatic Cancer
Carcinoma, Pancreatic Ductal
PDAC
Gastrointestinal Neoplasms
Intestinal Neoplasms
Esophageal cancer
Ampullary cancer
Gastric Cancer
Gynecological Cancer
Ovarian Cancer
Endometrial Cancer
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 222
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, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Detailed description: This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects 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:

* Subject must be ≥18 years of age.
* Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
* ECOG performance status 0 or 1
* Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation
* Adequate organ function

Exclusion Criteria:

* Primary central nervous system (CNS) tumors
* Active brain metastases
* Known impairment of GI function that would alter the absorption
* Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
* Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Adverse events
timeFrame: up to 3 years
measure: Dose Limiting Toxicities
timeFrame: The first 21 days (i.e. Cycle 1)
Secondary outcomes:
measure: Maximum Observed Blood Concentration of RMC-6291
timeFrame: 7 Cycles
measure: Time to Reach Maximum Blood Concentration of RMC-6291
timeFrame: 7 Cycles
measure: Area Under Blood Concentration Time Curve of RMC-6291
timeFrame: 7 Cycles
measure: Elimination Half-Life of RMC-6291
timeFrame: 7 Cycles
measure: Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing
timeFrame: 7 Cycles
measure: Overall Response Rate (ORR)
timeFrame: 3 years
measure: Duration of Response (DOR)
timeFrame: 3 years
measure: Disease Control Rate (DCR)
timeFrame: 3 years
measure: Time to Response (TTR)
timeFrame: 3 years
measure: Progression-Free Survival (PFS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Orange
country: United States
facility: UC Irvine Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Miami
country: United States
facility: University of Miami School of Medicine Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: MSK Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: San Antonio
country: United States
facility: START
state: Texas
city: Fairfax
country: United States
facility: Next Oncology Virginia
state: Virginia
city: Sydney
country: Australia
facility: Southside Cancer Care Centre
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health, Olivia Newton-John Cancer Research & Wellness Centre
state: Victoria
city: Warrnambool
country: Australia
facility: South West Health Care
state: Victoria
city: Hořovice
country: Czechia
facility: NH Hospital a.s.
city: Hradec Králové
country: Czechia
facility: Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove
city: Olomouc
country: Czechia
facility: Onkologicka klinika, Fakultni Nemocnice Olomouc
city: Angers
country: France
facility: ICO
city: Bordeaux
country: France
facility: CHU Bordeaux Hospital Saint-Andre
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nantes
country: France
facility: CHU Nantes
city: Strasbourg
country: France
facility: ICANS
city: Milano
country: Italy
facility: Istituto Europeo Oncologico
city: Milan
country: Italy
facility: S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Universitaria San Luigi Gonzaga
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Verona
country: Italy
facility: Centro Ricerche Cliniche di Verona s.r.l.
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Poznań
country: Poland
facility: Med - Polonia Sp. z o. o.
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii
city: Łódź
country: Poland
facility: Instytut MSF Sp zoo
city: Belgrade
country: Serbia
facility: MSB General Hospital
city: Belgrade
country: Serbia
facility: Clinical hospital center Bezanijska Kosa
city: Sremska Kamenica
country: Serbia
facility: Institute for pulmonary diseases Sremska Kamenica
city: Singapore
country: Singapore
facility: National Cancer centre Singapore
city: Barcelona
country: Spain
facility: NEXT Oncology IOB Hospital Quirónsalud
city: Barcelona
country: Spain
facility: ICO Hospitalet
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quirónsalud
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Kaohsiung
country: Taiwan
facility: E-DA hospital
state: Yanchao District
city: New Taipei City
country: Taiwan
facility: Taipei Tzu Chi Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok Noi
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc.
role: STUDY_DIRECTOR
References: