Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05462717
• Other study ID #: RMC-6291-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 19, 2022
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Revolution Medicines, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 222
• Est. completion date: December 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer (CRC)
• Colorectal Neoplasms
• Lung Neoplasms
• Non-Small Cell Lung Cancer (NSCLC)
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• RMC-6291
Oral tablet once or twice a day

Locations

Country	Name	City	State
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Austin Health, Olivia Newton-John Cancer Research & Wellness Centre	Heidelberg	Victoria
Australia	Southside Cancer Care Centre	Sydney	New South Wales
Australia	South West Health Care	Warrnambool	Victoria
Czechia	NH Hospital a.s.	Horovice
Czechia	Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove	Hradec Králové
Czechia	Onkologicka klinika, Fakultni Nemocnice Olomouc	Olomouc
France	ICO	Angers
France	CHU Bordeaux Hospital Saint-Andre	Bordeaux
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	CHU Nantes	Nantes
France	ICANS	Strasbourg
Italy	S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center	Milan
Italy	Istituto Europeo Oncologico	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Centro Ricerche Cliniche di Verona s.r.l.	Verona
Korea, Republic of	Korea University Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Sarawak General Hospital	Kuching
Poland	Instytut MSF Sp zoo	Lódz
Poland	Med - Polonia Sp. z o. o.	Poznan
Poland	Narodowy Instytut Onkologii	Warsaw
Serbia	Clinical hospital center Bezanijska Kosa	Belgrade
Serbia	MSB General Hospital	Belgrade
Serbia	Institute for pulmonary diseases Sremska Kamenica	Sremska Kamenica
Singapore	National Cancer centre Singapore	Singapore
Spain	ICO Hospitalet	Barcelona
Spain	NEXT Oncology IOB Hospital Quirónsalud	Barcelona
Spain	Clínica Universidad de Navarra	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitario Quirónsalud	Pozuelo De Alarcón
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	E-DA hospital	Kaohsiung	Yanchao District
Taiwan	Taipei Tzu Chi Hospital	New Taipei City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Siriraj Hospital	Bangkok Noi
Thailand	Chiang Mai University	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
United States	American Oncology Partners of Maryland	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Next Oncology Virginia	Fairfax	Virginia
United States	University of Miami School of Medicine Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	MSK Cancer Center	New York	New York
United States	UC Irvine Cancer Center	Orange	California
United States	UC Davis Cancer Center	Sacramento	California
United States	Next Oncology	San Antonio	Texas
United States	START	San Antonio	Texas
United States	UCSF	San Francisco	California
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Serbia,  Singapore,  Spain,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Number of participants with adverse events	up to 3 years
Primary	Dose Limiting Toxicities	Number of participants with dose limiting toxicities	The first 21 days (i.e. Cycle 1)
Secondary	Maximum Observed Blood Concentration of RMC-6291	Cmax	7 Cycles
Secondary	Time to Reach Maximum Blood Concentration of RMC-6291	Tmax	7 Cycles
Secondary	Area Under Blood Concentration Time Curve of RMC-6291	AUC	7 Cycles
Secondary	Elimination Half-Life of RMC-6291	t1/2	7 Cycles
Secondary	Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing	accumulation ratio	7 Cycles
Secondary	Overall Response Rate (ORR)	Overall response rate per RECIST v1.1	3 years
Secondary	Duration of Response (DOR)	Duration of response per RECIST v1.1	3 years
Secondary	Disease Control Rate (DCR)	Disease control rate per RECIST v1.1	3 years
Secondary	Time to Response (TTR)	Time to response per RECIST v1.1	3 years
Secondary	Progression-Free Survival (PFS)	Progression-free survival per RECIST v1.1	3 years