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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04468607
• Other study ID #: GO41751
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 31, 2020
• Est. completion date: January 2, 2026

Study information

• Verified date: June 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: January 2, 2026
• Est. primary completion date: January 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• BLYG8824A
BLYG8824A will be administered at a flat dose independent of body weight.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
United States	City of Hope	Duarte	California
United States	SCRI Oncology Partners	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Nature of DLTs		Approximately 48 months
Primary	Number of Patricipants with Adverse Events		Approximately 48 months
Primary	Number Of Cycles Received		Approximately 48 months
Primary	Dose Intensity		Approximately 48 months
Primary	Maximum Tolerated Dose(s) MTD(s) of BLYG8824A		Approximately 48 months
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)