Colorectal Cancer
Conditions
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.
Interventions
DRUGBLYG8824A
BLYG8824A will be administered at a flat dose independent of body weight.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose(s) MTD(s) of BLYG8824A | Approximately 48 months |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Approximately 48 months | 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) | Approximately 48 months | 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) | Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days) | — |
| 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) | — |
Countries
Australia, Spain, United States
Outcome results
None listed