Clinical trial NCT04929223: A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Official title: A Phase I/Ib Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-06-18
Enrollment: 542
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label, exploratory study is designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or combinations, in participants with metastatic colorectal cancer (mCRC) whose tumors are biomarker positive as per treatment arm-specific definition. Eligible participants with mCRC will be enrolled into specific treatment arms based on their biomarker assay results.


Eligibility criteria: Inclusion Criteria

* Signed cohort-specific Informed Consent Form
* Age \>= 18 years at time of signing Informed Consent Form
* Biomarker eligibility as determined by:

  * A validated test approved by local health authorities for detection of the specified biomarkers/mutations.
  * A validated test performed at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA) -certified or equivalently accredited diagnostic laboratory using a validated test for detection of the specified biomarkers.
  * Prior test results completed before signing cohort-specific Informed Consent Form or local test results generated prior to or during screening, and availability of a full report of the testing results OR
  * Blood-based FoundationOne Liquid CDx biomarker eligibility test result generated prior to or during screening or, in case of re-enrollment after treatment discontinuation, prior to starting a new anti-cancer therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of \<= 1
* Life expectancy \>= 3 months, as determined by the investigator
* Histologically confirmed adenocarcinoma originating from the colon or rectum
* Metastatic disease
* Prior therapies for metastatic disease
* Ability to comply with the study protocol, in the investigators judgment
* Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
* Baseline tumor tissue samples will be collected from all participants for exploratory biomarker research
* Adequate hematologic and organ function within 14 days prior to initiation of study treatment
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria

* Current participation or enrollment in another interventional clinical trial. Participants who are participating in the follow-up period of an interventional clinical trial are eligible for the study.
* Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Pregnant or breastfeeding, or intending to become pregnant during the study
* History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
* Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
* Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
* Uncontrolled tumor-related pain
* Uncontrolled or symptomatic hypercalcemia
* Clinically significant and active liver disease
* Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count greater than or equal to 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease or carcinomatous meningitis
* History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
* Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
* Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects participant compliance, or puts the patient at higher risk for treatment-related complications

Primary outcomes:
measure: Objective Response Rate
timeFrame: Approximately 84 months
Secondary outcomes:
measure: Duration of Response
timeFrame: Approximately 84 months
measure: Disease Control Rate
timeFrame: Approximately 84 months
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Approximately 84 months
measure: Plasma Concentrations of Divarasib
timeFrame: At pre-defined intervals from first administration of study drug up to approximately 84 months
measure: Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFOX
timeFrame: Approximately 84 months
measure: Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFIRI
timeFrame: Approximately 84 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Encinitas
country: United States
facility: cCare
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Norwich
country: United States
facility: Eastern Ct Hema/Onco Assoc
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Ctr
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Bronx
country: United States
facility: New York Cancer & Blood Specialists - Bronx
state: New York
city: New Hyde Park
country: United States
facility: New York Cancer & Blood Specialists - New Hyde Park
state: New York
city: New York
country: United States
facility: New York Cancer and Blood Specialists-Central Park Hematology & Oncology
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer & Blood Specialists
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Salem
country: United States
facility: Hematology Oncology Salem
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC - Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Inst.
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates
state: Washington
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: København Ø
country: Denmark
facility: Rigshospitalet, Onkologisk Klinik
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital
city: Dresden
country: Germany
facility: Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III
city: München
country: Germany
facility: Klinikum der Universität München, Campus Großhadern
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Napoli
country: Italy
facility: Università degli Studi della Campania Luigi Vanvitelli
state: Campania
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)
state: Lombardia
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV)
state: Veneto
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital;Dept of Med-Onc
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: