A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)

Metastatic Colorectal Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04929223
• Other study ID #: WO42758
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 22, 2021
• Est. completion date: April 15, 2026

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 422
• Est. completion date: April 15, 2026
• Est. primary completion date: September 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Signed cohort-specific Informed Consent Form

• Age >= 18 years at time of signing Informed Consent Form

• Biomarker eligibility as determined at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA)-certified or equivalently accredited diagnostic laboratory using a validated test

• 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 patients 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. Patients 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: Patients 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 patient 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 patient compliance, or puts the patient at higher risk for treatment-related complications

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Inavolisib
Inavolisib will be administered orally as per schedule specified in the respective arms.
• Bevacizumab
Bevacizumab IV will be administered as per schedule specified in the respective arm.
• Cetuximab
Cetuximab IV will be administered as per schedule specified in the respective arm.
• Atezolizumab
Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
• Tiragolumab
Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.
• SY-5609
SY-5609 will be administered by mouth as per schedule specified in the respective arm.
• Divarasib
Divarasib will be administered orally as per schedule specified in the respective arms.
• FOLFOX
FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.
• FOLFIRI
FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.

Locations

Country	Name	City	State
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Denmark	Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed	København Ø
Germany	Charité Universitätsmedizin Berlin; Hämatologie/Onkologie und Tumorimmunologie	Berlin
Germany	Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital; Klinik für Hämatologie und Onkologie	Bochum
Germany	Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden; Klinik und Poliklinik	Dresden
Germany	Universitätsklinikum Düsseldorf; Klinik für Gastroenterologie Infektologie u. Hepatologie	Düsseldorf
Germany	Asklepios Klinik Altona; Hämatologie, Onkologie, Palliativmedizin und Rheumatologie	Hamburg
Germany	SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm.	Heilbronn
Germany	Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III	München
Germany	Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I	Ulm
Italy	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck	Milano	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Università degli Studi della Campania Luigi Vanvitelli	Napoli	Campania
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima	Padova	Veneto
Italy	Policlinico Universitario Agostino Gemelli IRCCS; UOS Fase 1	Roma	Lazio
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii	Kraków
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzia? Onkologii Klinicznej i Doswiadczalnej	Poznan
Poland	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz	Warszawa
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Taiwan	National Cheng Kung University Hospital; Oncology	Tainan
Taiwan	Taipei Veterans General Hospital; Department of Oncology	Taipei City
Taiwan	National Taiwan University Hospital; Oncology	Zhongzheng Dist.
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	Royal Free Hospital; Dept of Oncology	London
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc; .	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital; Institute of Cancer Research	Sutton
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Mary Bird Perkins Cancer Ctr	Baton Rouge	Louisiana
United States	UAB Comprehensive Cancer Center; Clinical Studies Unit	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New York Cancer & Blood Specialists	Bronx	New York
United States	New York Cancer & Blood Specialists - Bronx	Bronx	New York
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	cCare	Encinitas	California
United States	Mayo Clinic in Florida; Department of Hematology	Jacksonville	Florida
United States	Lumi Research	Kingwood	Texas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Sarah Cannon Research Institute / Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	New York Cancer & Blood Specialists - New Hyde Park	New Hyde Park	New York
United States	New York Cancer and Blood Specialists-Central Park Hematology & Oncology	New York	New York
United States	Eastern Ct Hema/Onco Assoc; Dept of Oncology	Norwich	Connecticut
United States	Stanford Cancer Center	Palo Alto	California
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	UPMC - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Hematology Oncology Salem	Salem	Oregon
United States	Swedish Cancer Inst.	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Germany,  Italy,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Defined as the proportion of patients with a complete response or partial response, as determined by the investigator according to RECIST v1.1	Approximately 60 months
Secondary	Duration of Response	Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1	Approximately 60 months
Secondary	Disease Control Rate	Defined as the proportion of patients with stable disease, or a complete or partial response, as determined by the investigator according to RECIST v1.1	Approximately 60 months
Secondary	Percentage of Participants with Adverse Events (AEs)	Percentage of participants with adverse events.	Approximately 60 months
Secondary	Plasma Concentrations of Divarasib	Plasma concentration of divarasib for divarasib + cetuximab + FOLFOX, divarasib + cetuximab, and divarasib + cetuximab+ FOLFIRI treatment arms.	At pre-defined intervals from first administration of study drug up to approximately 60 months