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)

NCT05673876 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GA43861ISRCTN27200385
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

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).

Conditions

Acute Graft-versus-host Disease

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (4)

• Overall Response Rate (ORR) on Day 29

  Up to Day 29

• Duration of Response (DOR)

  From Day 29 up to end of study (up to 9 months)

• Percentage of Participants With aGVHD Flares by Day 56

  Baseline up to Day 56

• Percentage of Participants With Non-relapse Mortality (NRM) by Day 180

  Baseline up to Day 180

Study Arms (2)

GDC-8264, 35 mg

EXPERIMENTAL

Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days.

Drug: GDC-8264

GDC-8264, 75 mg

EXPERIMENTAL

Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days.

Drug: GDC-8264

Interventions

GDC-8264 DRUG

GDC-8264 tablets will be administered as per the schedule specified in the respective arms.

GDC-8264, 35 mg; GDC-8264, 75 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (4)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech Inc

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 6, 2023
• Study Start: April 6, 2023
• Primary Completion: January 15, 2024
• Study Completion: January 15, 2024
• Last Updated: May 28, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)