A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: BLYG8824A

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GO41751 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre; Medical Oncology
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital; Malignant Haematology & Stem Cell Transplant Service
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-Escalation Stage; Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).	Drug: BLYG8824A; BLYG8824A will be administered at a flat dose independent of body weight.
Experimental: Dose-Expansion Stage; 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.	Drug: BLYG8824A; BLYG8824A will be administered at a flat dose independent of body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and Nature of DLTs	Approximately 48 months
Number of Patricipants with Adverse Events	Approximately 48 months
Number Of Cycles Received	Approximately 48 months
Dose Intensity	Approximately 48 months
Maximum Tolerated Dose(s) MTD(s) of BLYG8824A	Approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of BLYG8824A		At predifined interevals from Cycle 1 Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
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)	Approximately 48 months
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	Approximately 48 months
Presence of Anti-drug Antibodies (ADAs)		Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Estimated): January 2, 2026
• Study Completion (Estimated): January 2, 2026

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 13, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 16, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: GO41751

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No