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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: BLYG8824A


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |