A Phase Ib/II, Multicenter, Open-label, Single-arm Study to Assess the Safety and Efficacy of GFH009 in Combination With Zanubrutinib in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Genfleet Therapeutics (Shanghai) Inc.2 sites in 1 country51 target enrollmentMarch 20, 2024

ConditionsLarge B-cell Lymphoma

InterventionsGFH009 Zanubrutinib

DrugsGFH009 Zanubrutinib

Overview

Phase: Phase 1
Intervention: GFH009
Conditions: Large B-cell Lymphoma
Sponsor: Genfleet Therapeutics (Shanghai) Inc.
Enrollment: 51
Locations: 2
Primary Endpoint: Phase Ib: adverse events(AEs)
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicentre, open-label phase Ib/II study. The purpose of the study is to assess the safety and efficacy of GFH009 in combination with Zanubrutinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Registry

clinicaltrials.gov

Start Date

March 20, 2024

End Date

December 31, 2026

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Genfleet Therapeutics (Shanghai) Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 18 years old.
•Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including: DLBCL, not specified (NOS), T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), high-grade B-cell lymphoma, or large B-cell lymphoma transformed from indolent B-cell lymphoma (including but not limited to Richter syndrome, transformed follicular lymphoma, transformed MZL) (2016 WHO classification).
•Relapse or refractory after receiving 2\~4 systemic treatment regimens, at least one of which contains anthracyclines and Rituximab.
•Must have a measurable lesion.
•The patient is not suitable to receive stem cell transplantation judged by the investigator.
•The Eastern Cooperative Oncology Group (ECOG) performance status score (PS) is 0\~
•Have adequate organ function, including:
•i. Hematopoietic function: absolute neutrophil count (ANC) ≥1.0×109/L, platelet count (PLT) ≥75×109/L and hemoglobin (Hgb) ≥ 80 g/L.
•ii. Liver function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
•iii. Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, or serum creatinine clearance ≥ 50 mL/min when Cr \> 1.5× ULN.

Exclusion Criteria

•Primary or secondary central nervous system (CNS) lymphoma.
•Received chemotherapy, targeted therapy, endocrine therapy, immunotherapy, Chinese patent medicine with anti-tumor effect and other investigational drugs or device therapy within 28 days or 5 half-lives (whichever is shorter), or received therapeutic or palliative radiotherapy within 14 days, or received CAR-T therapy within 12 weeks prior to the administration of the study drugs.
•Patients with primary resistance to CDK9 or BTK inhibitors.
•Has a history of organ transplantation or allogeneic stem cell transplantation. Patients who have undergone autologous stem cell transplantation within 6 months.
•Other malignancies within 2 years prior to study entry, excluding appropriately treated carcinoma in situ of the cervix, focal squamous cell carcinoma of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, and superficial non-muscle-invasive urothelial carcinoma.
•Have significant diseases of the cardiovascular system or significant acute or chronic infection. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. Presence of significant gastrointestinal disorders. Current clinically significant interstitial lung disease, radiation pneumonitis, or drug-associated pneumonia requiring treatment. Accompanied by other poorly controlled systemic diseases, such as hypertension, diabetes mellitus, etc.
•Has a history of bleeding disorder or a history of spontaneous bleeding requiring blood transfusion or other medical intervention. Active bleeding within 2 months prior to the first dose.
•Surgical procedures (excluding needle biopsies) that may affect the administration or study evaluation of this study within 28 days prior to the first dose.
•Patients who have been treated with prednisone (or equivalent doses of glucocorticoids) at \>20 mg/day for anti-tumor purposes within 7 days, or who require long-term use of glucocorticoids for non-anti-tumor therapy.
•Ongoing medical treatment with a potent inhibitor or inducer of CYP3A is required.

Arms & Interventions

Phase 1b:GFH009 & Zanubrutinib

Intervention: GFH009

Phase 1b:GFH009 & Zanubrutinib

Intervention: Zanubrutinib

Phase 2: GFH009 & Zanubrutinib

Intervention: GFH009

Phase 2: GFH009 & Zanubrutinib

Intervention: Zanubrutinib

Outcomes

Primary Outcomes

Phase Ib: adverse events(AEs)

Time Frame: From Screening (Day -28 to Day-1) to 30 days ±7 days after the last dose, or until the start of a new anti-tumor therapy，assessed up to 32 months

Incidence of DLT events, incidence and severity of AEs and serious adverse events (SAEs), Electrocardiogram changes

Phase II: ORR

Time Frame: From Screening (Day -28 to Day-1) to 30 days ±7 days after the last dose,or until the start of a new anti-tumor therapy, assessed up to 32 months

ORR(Objective Response Rate) as assessed by the investigator according to the 2014 Lugano standards