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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04929223
Collaborator
(none)
220
Enrollment
35
Locations
5
Arms
38.3
Anticipated Duration (Months)
6.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
220 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Oct 22, 2021
Anticipated Primary Completion Date :
May 31, 2024
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Inavolisib + Cetuximab

Participants will receive 9 milligrams (mg) of inavolisib by mouth once daily (QD) on Days 8-28 of Cycle 1, then QD on Days 1-28 from Cycle 2 onwards (1 cycle=28 days). Participants will also receive cetuximab intravenous (IV) infusion 400 mg/m2 body surface area on Day 1 of Cycle 1. All subsequent weekly (QW) doses will be 250 mg/m2 each.

Drug: Inavolisib
Inavolisib will be administered orally as per schedule specified in the respective arms.

Drug: Cetuximab
Cetuximab IV will be administered as per specified in the respective arm.
Experimental: Inavolisib + Bevacizumab

Participants will receive 9 mg of inavolisib by mouth QD combined with bevacizumab 15 milligram/kilogram (mg/kg) IV once every three weeks (Q3W) on Day 1 of each cycle (1 cycle=21 days).

Drug: Inavolisib
Inavolisib will be administered orally as per schedule specified in the respective arms.

Drug: Bevacizumab
Bevacizumab IV will be administered as per specified in the respective arm.
Other Names:
  • Avastin

    		•
    Experimental: Atezolizumab + Tiragolumab + Bevacizumab

    Participants will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle, combined with Tiragolumab at a dose of 600 mg IV infusion on Day 1 of each cycle and Bevacizumab IV infusion at a dose of 15 mg/kg on Day 1 of each cycle. (Cycle length=21 days)

    Drug: Bevacizumab
    Bevacizumab IV will be administered as per specified in the respective arm.
    Other Names:
  • Avastin

    • Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other Names:
  • Tecentriq

    • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per specified in the respective arm.
    Experimental: Atezolizumab + Tiragolumab

    Participants will receive 1200 mg of atezolizumab by IV infusion on Day 1 of each cycle combined with tiragolumab 600 mg IV infusion on Day 1 of each cycle. (Cycle length=21 days)

    Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other Names:
  • Tecentriq

    • Drug: Tiragolumab
    Tiragolumab IV infusion will be administered as per specified in the respective arm.
    Experimental: Atezolizumab + SY-5609

    Participants will receive 1680 mg of atezolizumab by IV infusion on Day 1 of each cycle Q4W in repeated 28-day cycles combined with SY-5609 at a dose of 3, 4, or 5 mg by mouth for 7 days, followed by 7 days off. (Cycle length=28 days)

    Drug: Atezolizumab
    Atezolizumab IV infusion will be administered as per specified in the respective arm.
    Other Names:
  • Tecentriq

    • Drug: SY-5609
    SY-5609 will be administered by mouth as per specified in the respective arm.

    Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate [Approximately 36 months]

      Defined as the proportion of patients with a complete response or partial response, as determined by the investigator according to RECIST v1.1

    Secondary Outcome Measures

    1. Duration of Response [Approximately 36 months]

      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

    2. Disease Control Rate [Approximately 36 months]

      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

    3. Percentage of Participants with Adverse Events (AEs) [Approximately 36 months]

      Percentage of participants with adverse events.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Signed next-generation sequencing (NGS) Biomarker Eligibility 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)

    • Availability of an archival tissue sample for exploratory biomarker research

    • Adequate hematologic and organ function within 14 days prior to initiation of study treatment

    • For women of childbearing potential: Must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment and agreement to remain abstinent 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

    • 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

    • Known HIV infection

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Arizona Phoenix Arizona United States 85259
    2 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    3 USC Norris Cancer Center Los Angeles California United States 90033
    4 Cedars-Sinai Medical Center Los Angeles California United States 90048
    5 UCLA Los Angeles California United States 90095
    6 Hoag Memorial Hospital Presbyterian Newport Beach California United States 92663
    7 Stanford Cancer Center Stanford California United States 94305-5820
    8 University of Colorado Cancer Center Aurora Colorado United States 80045
    9 Mayo Clinic in Florida; Department of Hematology Jacksonville Florida United States 32224
    10 Moffitt Cancer Center Tampa Florida United States 33612
    11 Massachusetts General Hospital Boston Massachusetts United States 02114
    12 Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine Boston Massachusetts United States 02215
    13 Mayo Clinic Rochester Rochester Minnesota United States 55902
    14 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    15 Duke University Medical Center Durham North Carolina United States 27705
    16 SCRI-Tennessee Oncology Nashville Tennessee United States 37203
    17 Vanderbilt University Medical Center Nashville Tennessee United States 37212
    18 Medical Oncology Associates Spokane Washington United States 99208
    19 Princess Margaret Cancer Center Toronto Ontario Canada M5G 2M9
    20 Jewish General Hospital; Clinical Research Unit Montreal Quebec Canada H3T 1E2
    21 McGill University Health Center Montreal Quebec Canada H4A 3J1
    22 Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1 Milano Lombardia Italy 20133
    23 Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck Milano Lombardia Italy 20162
    24 IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima Padova Veneto Italy 35128
    25 Seoul National University Bundang Hospital Seongnam-si Korea, Republic of 13605
    26 Seoul National University Hospital Seoul Korea, Republic of 03080
    27 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    28 Asan Medical Center Seoul Korea, Republic of 05505
    29 Samsung Medical Center Seoul Korea, Republic of 06351
    30 Vall d´Hebron Institute of Oncology (VHIO), Barcelona Barcelona Spain 08035
    31 START Madrid. Centro Integral Oncologico Clara Campal; CIOCC Madrid Spain 28050
    32 Addenbrookes Hospital Cambridge United Kingdom CB2 0QQ
    33 Velindre Cancer Centre Cardiff United Kingdom CF14 2TL
    34 Sarah Cannon Research Institute London United Kingdom W1G 6AD
    35 Imperial College Healthcare NHS Trust London United Kingdom W2 1NY

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04929223
    Other Study ID Numbers:
    • WO42758
    First Posted:
    Jun 18, 2021
    Last Update Posted:
    Aug 1, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Colorectal Neoplasms
    Bevacizumab
    Cetuximab
    Atezolizumab

    Study Results

    No Results Posted as of Aug 1, 2022