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 Overview
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Brief Summary
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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).

Official Title
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A Phase Ib, Open-label, Randomized, Dose-finding, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of GDC-8264 in Combination With Standard of Care in the Treatment of Acute Graft-versus-Host Disease in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Acute Graft-versus-host Disease

Intervention / Treatment
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* Drug: GDC-8264


Participation Criteria
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Eligibility Criteria
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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: 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 Prior receipt of more than one allogeneic HSCT Prior receipt of solid organ transplantation that are target organs for aGVHD (e.g., liver transplant) Prior systemic treatment for aGVHD, except for the standard of care corticosteroid treatment initiated as part of this trial Diagnosis of chronic GVHD or overlap syndrome 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) Severe organ dysfunction (e.g., acute liver failure, renal failure requiring dialysis, ventilator support, or vasopressor therapy) 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

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GDC-8264, 35 mg<br>Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days. | Drug: GDC-8264<br>* GDC-8264 tablets will be administered as per the schedule specified in the respective arms.<br>|
| Experimental: GDC-8264, 75 mg<br>Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days. | Drug: GDC-8264<br>* GDC-8264 tablets will be administered as per the schedule specified in the respective arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall 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 |