A Study to Assess the Safety and Pharmacokinetics of GDC-8264 in Combination With Standard of Care in Participants With Acute Graft-Versus-Host Disease (aGVHD)
Study Details
Study Description
Brief Summary
The primary purpose of the study is to assess the safety and pharmacokinetics (PK) of GDC-8264 in participants with acute graft-versus-host disease (aGVHD).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GDC-8264, 35 mg Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days. |
Drug: GDC-8264
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.
|
| Experimental: GDC-8264, 75 mg Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days. |
Drug: GDC-8264
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with At Least One Adverse Events (AEs) and As per Severity of AEs [Screening up to end of study (up to approximately 3 years)]
- Plasma Concentration of GDC-8264 [From Day 1 up to Day 57]
Secondary Outcome Measures
- Objective Response Rate (ORR) [Up to Day 29]
- Duration of Response (DOR) [From Day 29 up to end of study (up to approximately 3 years)]
- Percentage of Participants with aGVHD Flares [Baseline up to Day 56]
- Percentage of Participants with Non-relapse Mortality (NRM) [Baseline up to Day 180]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of post-allogeneic hematopoietic stem cell transplantation (HSCT) aGVHD at screening
-
Evidence of engraftment post-transplant
-
Diagnosis of high-risk aGVHD, per refined Minnesota high-risk aGVHD criteria during screening
-
Initiation of treatment with systemic corticosteroids for aGVHD at a dose of prednisone ≥2 milligrams per kilograms per day (mg/kg/day) by orally (PO) or methylprednisolone ≥2 mg/kg/day intravenously (or equivalent) in divided doses at diagnosis and up to 3 days prior to or on the same day as initiation of GDC-8264 (Day 1), with no taper planned prior to Day 3
Exclusion Criteria:
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Evidence of relapsed, progressing, or persistent malignancy, or treatment for relapse after transplant, or requirement for rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse
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Prior receipt of more than one allogeneic HSCT
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Prior systemic treatment for aGVHD, except for the standard of care corticosteroid treatment initiated as part of this trial
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Diagnosis of chronic GVHD or overlap syndrome
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Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment, or persistently positive blood cultures despite treatment, or any other evidence of severe sepsis)
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Severe organ dysfunction (e.g., acute liver failure, renal failure requiring dialysis, ventilator support, or vasopressor therapy)
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Initiation or planned use of a marketed small molecule (excluding corticosteroids) or biologic therapy as treatment for aGVHD from the start of screening through the treatment period
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GA43861
- ISRCTN27200385