A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BLYG8824A
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- ECOG performance status of 0 or 1
- Life expectancy of at least 12 weeks
- Histologically or cytologically documented invasive CRC: incurable, unresectable, locally advanced or metastatic CRC previously treated with multimodality therapy or mCRC
- Locally advanced or metastatic CRC that has relapsed or is refractory to established therapies
- Prior disease progression (or intolerance) following oxaliplatin, irinotecan, fluoropyrimidines, and anti-EGFR monoclonal antibodies
- An archival tissue specimen or fresh baseline biopsy (when archival is not available) is required for enrollment into the study
- Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Non-measurable evaluable disease is acceptable for dose-escalation.
- Adequate hematologic and end organ function
- Acute, clinically significant treatment-related toxicity from prior therapy resolved to Grade ≤ 1 prior to study entry
Expansion Cohort-Specific Inclusion Criteria
- MSS or MSI-L disease as determined by polymerase chain reaction (PCR) and/or IHC
- Measurable disease by RECIST v1.1 with at least one measurable target lesion in the expansion cohort
- Progression must have occurred during or after most recent treatment for locally advanced or metastatic colorectal cancer
Exclusion Criteria:
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of BLYG8824A
- Significant cardiopulmonary dysfunction
- Known clinically significant liver disease
- Positive serologic or PCR test results for acute or chronic HBV infection
- Acute or chronic HCV infection
- HIV seropositivity
- Poorly controlled Type 2 diabetes mellitus
- Current treatment with medications that are well known to prolong the QT interval
- Primary CNS malignancy, untreated CNS metastases, or active CNS metastases
- Leptomeningeal disease
- Spinal cord compression that has not been definitively treated with surgery and/or radiation
- History of autoimmune disease
- Prior allogeneic stem cell or solid organ transplantation
Sites / Locations
- City of HopeRecruiting
- Sarah Cannon Research InstituteRecruiting
- Peter MacCallum Cancer Centre; Medical OncologyRecruiting
- The Alfred Hospital; Malignant Haematology & Stem Cell Transplant ServiceRecruiting
- Princess Margaret Cancer Centre; Clinical Trials PharmacyRecruiting
- Clinica Universitaria de NavarraRecruiting
- Hospital Universitario Vall d'Hebron - PPDSRecruiting
- START Madrid-FJD, Hospital Fundacion Jimenez DiazRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose-Escalation Stage
Dose-Expansion Stage
Arm Description
Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).
Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial.
Outcomes
Primary Outcome Measures
Incidence and Nature of DLTs
Number of Patricipants with Adverse Events
Number Of Cycles Received
Dose Intensity
Maximum Tolerated Dose(s) MTD(s) of BLYG8824A
Secondary Outcome Measures
Serum Concentration of BLYG8824A
Overall Response Rate (ORR)
ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Duration of Response (DOR)
Duration of response (DOR), 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
Presence of Anti-drug Antibodies (ADAs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04468607
Brief Title
A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer
Official Title
A Phase I, Open-Label, Dose-Escalation Study Of The Safety And Pharmacokinetics Of BLYG8824A Administered Intravenously In Patients With Locally Advanced Or Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 31, 2020 (Actual)
Primary Completion Date
January 2, 2026 (Anticipated)
Study Completion Date
January 2, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of BLYG8824A in patients with locally advanced or metastatic colorectal cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Masking Description
Open Label
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose-Escalation Stage
Arm Type
Experimental
Arm Description
Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).
Arm Title
Dose-Expansion Stage
Arm Type
Experimental
Arm Description
Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial.
Intervention Type
Drug
Intervention Name(s)
BLYG8824A
Intervention Description
BLYG8824A will be administered at a flat dose independent of body weight.
Primary Outcome Measure Information:
Title
Incidence and Nature of DLTs
Time Frame
Approximately 48 months
Title
Number of Patricipants with Adverse Events
Time Frame
Approximately 48 months
Title
Number Of Cycles Received
Time Frame
Approximately 48 months
Title
Dose Intensity
Time Frame
Approximately 48 months
Title
Maximum Tolerated Dose(s) MTD(s) of BLYG8824A
Time Frame
Approximately 48 months
Secondary Outcome Measure Information:
Title
Serum Concentration of BLYG8824A
Time Frame
At predifined interevals from Cycle 1 Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
Title
Overall Response Rate (ORR)
Description
ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time Frame
Approximately 48 months
Title
Duration of Response (DOR)
Description
Duration of response (DOR), 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
Time Frame
Approximately 48 months
Title
Presence of Anti-drug Antibodies (ADAs)
Time Frame
Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
ECOG performance status of 0 or 1
Life expectancy of at least 12 weeks
Histologically or cytologically documented invasive CRC: incurable, unresectable, locally advanced or metastatic CRC previously treated with multimodality therapy or mCRC
Locally advanced or metastatic CRC that has relapsed or is refractory to established therapies
Prior disease progression (or intolerance) following oxaliplatin, irinotecan, fluoropyrimidines, and anti-EGFR monoclonal antibodies
An archival tissue specimen or fresh baseline biopsy (when archival is not available) is required for enrollment into the study
Measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Non-measurable evaluable disease is acceptable for dose-escalation.
Adequate hematologic and end organ function
Acute, clinically significant treatment-related toxicity from prior therapy resolved to Grade ≤ 1 prior to study entry
Expansion Cohort-Specific Inclusion Criteria
MSS or MSI-L disease as determined by polymerase chain reaction (PCR) and/or IHC
Measurable disease by RECIST v1.1 with at least one measurable target lesion in the expansion cohort
Progression must have occurred during or after most recent treatment for locally advanced or metastatic colorectal cancer
For patients enrolled in either a dedicated biopsy cohort or other expansion cohorts where biopsy is clinically feasible, willingness to consent to mandatory fresh pretreatment and on-treatment biopsies of safely accessible tumor lesions
Exclusion Criteria:
Pregnant or breastfeeding, or intending to become pregnant during the study or within 4 months after the final dose of BLYG8824A
Significant cardiopulmonary dysfunction
Known clinically significant liver disease
Positive serologic or PCR test results for acute or chronic HBV infection
Acute or chronic HCV infection
HIV seropositivity
Poorly controlled Type 2 diabetes mellitus
Current treatment with medications that are well known to prolong the QT interval
Primary CNS malignancy, untreated CNS metastases, or active CNS metastases
Leptomeningeal disease
Spinal cord compression that has not been definitively treated with surgery and/or radiation
History of autoimmune disease
Prior allogeneic stem cell or solid organ transplantation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO41751 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Peter MacCallum Cancer Centre; Medical Oncology
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
The Alfred Hospital; Malignant Haematology & Stem Cell Transplant Service
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Centre; Clinical Trials Pharmacy
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Clinica Universitaria de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Vall d'Hebron - PPDS
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer
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