DZD8586 Combination Therapy in Patients With Diffuse Large B-cell Lymphoma (TAI-SHAN12)

Official title

A Phase Ib/II, Multicenter Study to Evaluate the Efficacy and Safety of DZD8586 Combination Therapy in Diffuse Large B-cell Lymphoma

Overview

This study will treat patients with diffuse large B-cell lymphoma (DLBCL). It will assess the anti-tumor efficacy and safety of DZD8586 combination therapy by using objective response rate and the incidence and severity of adverse events. It will also measure the levels of DZD8586 in the body when combined with immunochemotherapy regimens.

Interventions

• Drug DZD8586+R-CHOP
  DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with R-CHOP (Rituximab: 375 mg/m2, IV, d1; Cyclophosphamide: 750 mg/m2, IV, d1; Doxorubicin: 50 mg/m2, IV, d1; Vincristine: 1.4 mg/m2, IV, d1; Prednisone: 100 mg, po, d1-5) in a 21-day cycle for 6 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.
• Drug DZD8586+R-GemOx
  DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with R-GemOx (Rituximab: 375 mg/m2, IV, d1; Gemcitabine: 1000 mg/m2, IV, d1; Oxaliplatin: 100 mg/m2, IV, d1) in a 21-day cycle for 8 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.
• Drug DZD8586+BR
  DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with BR (Bendamustine: 90 mg/m2, IV, d1-d2; Rituximab: 375 mg/m2, IV, d1) in a 21-day cycle for 6 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.

Primary outcome measures

• Part A: Incidence and severity of adverse events [Time frame: Approximately 5 years]
• Part B: Objective response rate (ORR) [Time frame: Approximately 5 years]

Secondary outcome measures (12)

• Part A: Objective response rate (ORR) [Time frame: Approximately 5 years]
• Part A: Complete response rate (CRR) [Time frame: Approximately 5 years]
• Part A: Time to response (TTR) [Time frame: Approximately 5 years]
• Part A: Duration of Response (DoR) [Time frame: Approximately 5 years]
• Part A: Progression-Free Survival (PFS) [Time frame: Approximately 5 years]
• Part A: Overall Survival (OS) [Time frame: Approximately 5 years]
• Part B: Incidence and severity of adverse events [Time frame: Approximately 5 years]
• Part B: Complete response rate (CRR) [Time frame: Approximately 5 years]
• Part B: Time to response (TTR) [Time frame: Approximately 5 years]
• Part B: Duration of Response (DoR) [Time frame: Approximately 5 years]
• Part B: Progression-Free Survival (PFS) [Time frame: Approximately 5 years]
• Part B: Overall Survival (OS) [Time frame: Approximately 5 years]

Eligibility criteria

Inclusion criteria

• Cohort 1:

• Patients with pathologically confirmed DLBCL who have not received prior anti-lymphoma therapy.
• Disease stage II to IV by Ann Arbor Classification.
• Life expectancy ≥ 12 months.
• Cohort 2, 3:

• Pathologically confirmed DLBCL patients who have received adequate first-line treatment containing CD20 monoclonal antibody and anthracyclines (such as R-CHOP-like regimen).
• Relapsed or refractory to first-line R-CHOP-like regimen.
• For patients who have received only one line of therapy, if the patient has not received autologous stem cell transplantation, the investigator needs to assess as unsuitable or the patient refuses intensive chemotherapy and hematopoietic stem cell transplantation.
• Life expectancy ≥ 6 months.
• Patients must also meet all of the following criteria to be included in this study:

• All patients must provide a signed and dated written informed consent prior to any study-specific procedure, sampling, and analysis.
• Patients must be ≥ 18 years of age at the time of informed consent.
• ECOG status score of 0 to 2.
• Presence of at least one radiologically measurable lesion in 2 perpendicular directions as assessed by CT or MRI and a positive lesion on PET/CT scan consistent with a tumor site identified by CT or MRI.
• Adequate bone marrow hematopoietic reserve and organ function.
• No uncontrolled medical complications.
• Patients should be able to follow the relevant requirements of this study for medication and follow-up.
• Willing to comply with contraceptive restrictions.

Exclusion criteria

• Cohort 2, 3:

a. Hematopoietic stem cell transplantation, cell therapy, or gene therapy within 90 days prior to first dose. Radiation therapy within 14 days prior to first dose. Chemotherapy and small-molecule targeted therapy were not terminated within 5 half-lives before the first dose; macromolecule drug therapy (such as antibody therapy) was not terminated within 28 days before the first dose.

• All patients should not be included in this study if they have any of the following conditions:

• Indolent lymphoma-transformed DLBCL, primary mediastinal lymphoma, lymphoma involving the central nervous system, or DLBCL with MYC and BCL2 rearrangements.
• Prior use of BTK inhibitors.
• Vaccination with live attenuated vaccines or viral vector vaccines within 4 weeks prior to enrollment.
• Currently taking vitamin K antagonists, taking 2 or more antiplatelet/anticoagulant drugs at the same time, drugs/herbs or supplements known to potently induce or inhibit CYP3A enzyme activity, proton pump inhibitor drugs, anti-tumor traditional Chinese medicine or failing to meet the protocol-specified withdrawal time before administration in this study.
• Major surgery within 4 weeks or anticipated surgery after the start of this study. Or insufficiently recovered from any toxicity and/or complications of previous intervention.
• Clinically significant cardiac disorders. History of thrombotic diseases, stroke or intracranial hemorrhage within 6 months.
• Active infectious diseases.
• Intractable nausea and vomiting that cannot be well controlled by supportive treatment, chronic gastrointestinal diseases, dysphagia, or previous surgical resection of the intestinal segment may affect the adequate absorption of the drug.
• The patient has been diagnosed with other malignant diseases other than B-cell lymphoma within the past 2 years.
• Patients with hypersensitivity to DZD8586 drug excipients or other chemical analogues.
• Patients with severe or uncontrolled systemic diseases, including poorly controlled hypertension and active bleeding constitution.
• Serious medical or psychiatric illness that could affect participation in the study or could compromise the ability to consent
• Women who are pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 13 centers

• Peking University Third Hospital — Beijing
• Hunan Cancer Hospital — Changsha
• West China Hospital of Sichuan University — Chengdu
• Guangdong Provincial People's Hospital — Guangzhou
• Sun Yat-sen University Cancer Center — Guangzhou
• Zhujiang Hospital of Southern Medical University — Guangzhou
• The Second Affiliated Hospital Zhejiang University School of Medicine — Hangzhou
• Anhui Provincial Cancer Hospital — Hefei
• … and 5 more centers

Identifiers

NCT: NCT07059650 · DZ2024B0001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗