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)

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

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).

Study Overview

• Status: Completed
• Conditions: Acute Graft-versus-host Disease
• Intervention / Treatment: Drug: GDC-8264

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From signing informed consent form until 28 days after the final dose of GDC-8264 (up to 9 months)
Plasma Concentration of GDC-8264	Plasma concentration of GDC-8264 at specified timepoints was determined.	Predose, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose on Days 1 and 4; Predose on Days 8, 15, 22, 29
Maximum Plasma Concentration (Cmax) of GDC-8264	Steady-state (SS) PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)
Time to Reach Maximum Plasma Concentration (Tmax) of GDC-8264	SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of GDC-8264	SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)
Terminal Half-life (T1/2) of GDC-8264	SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)
Apparent Clearance (CL/F) of GDC-8264	SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)
Apparent Volume of Distribution (Vz/F) of GDC-8264	SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.	Day 1 and SS visit (any time between Day 4 to Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) on Day 29	ORR=percentage of participants with complete response (CR), very good partial response (VGPR), or partial response (PR) as determined by investigator. CR=all target organs evaluated as Mount Sinai Acute GVHD International Consortium (MAGIC) aGVHD Stage 0 [Skin- no GVHD rash; Liver - bilirubin <2 milligrams/decilitres (mg/dL); Upper gastrointestinal (GI) tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: < 500 mL/day or <3 episodes/day (adults), <10 mL/kilograms (kg)/day or <4 episodes/day]. VGPR=resolution of signs & symptoms i.e. no rash/residual erythematous rash involving < 25% of body surface, without (w/o) bullae; bilirubin <2 mg/dL or <25% of baseline at screening; toleration of food/enteral feeding; predominantly formed stools; no overt GI bleeding/abdominal cramping; no more than occasional nausea/vomiting. PR=improvement in one/more target organs (skin, liver, upper GI tract, lower GI tract) involved with aGVHD symptoms w/o worsening in others.	Up to Day 29
Duration of Response (DOR)	DOR was defined astime from response (CR, VGPR or PR) on Day 29 to aGVHD progression from nadir in any organ, new systemic therapy for aGVHD, or death from any cause (whichever occurs first), as determined by the investigator. CR=all target organs evaluated as MAGIC aGVHD Stage 0 [Skin- no GVHD rash; Liver - bilirubin <2 mg/dL; Upper GI tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: < 500 mL/day or <3 episodes/day (adults), <10 mL/kg/day or <4 episodes/day]. VGPR=resolution of signs & symptoms i.e. no rash or residual erythematous rash involving < 25% of body surface, without bullae; bilirubin <2 mg/dL or <25% of baseline at screening; toleration of food/enteral feeding; predominantly formed stools; no overt GI bleeding or abdominal cramping; no more than occasional nausea or vomiting. PR=improvement in one or more target organs (skin, liver, upper GI tract, lower GI tract) involved with aGVHD symptoms without worsening in others.	From Day 29 up to end of study (up to 9 months)
Percentage of Participants With aGVHD Flares by Day 56	aGVHD flare was defined as an increase in aGVHD target organ stage by at least one stage for at least 3 days that requires either addition of a new line of systemic treatment or increase in corticosteroid dose > 0.25 mg/kg/day.	Baseline up to Day 56
Percentage of Participants With Non-relapse Mortality (NRM) by Day 180	NRM was defined as any death that occurred after onset of aGVHD that was not attributable to relapse of the underlying primary disease was considered a non-relapse death.	Baseline up to Day 180

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2023
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): January 15, 2024

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: GA43861; ISRCTN27200385 (Other Identifier: ISRCTN (United Kingdom))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No