DZD8586 in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This study will treat patients with B-NHL who have relapsed, progressed, or were intolerant to systemic therapy progressed following prior therapy. This study will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and assess its anti-cancer activity as monotherapy.

Official Title
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A Phase 1, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Efficacy of DZD8586 in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (B-NHL)

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: DZD8586


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants who have provided ICF with age ≥ 18 yrs ECOG performance 0-2, no deterioration in the past 2 weeks Participants with relapsed or refractory B-NHL must have cytologically or histologically confirmed B-cell lymphoma Adequate bone marrow reserve and organ system functions Participants willing to comply with contraceptive restrictions Exclusion Criteria: Any unresolved > Grade 1 adverse event at the time of starting study treatment with the exception of alopecia. Prior history of allogeneic hematopoietic stem cell transplantation Stem cell transplantation, cell therapy, or gene therapy within 90 days. Approved small molecule therapy within 5 half-lives, investigational small molecule therapy within 14 days. Monoclonal antibodies and antibody-drug conjugates within 28 days Radiation therapy within 1 weeks Live attenuated vaccines or viral vector vaccines within 4 weeks. Major surgery or significant traumatic injury within 4 weeks. History of stroke or intracranial hemorrhage within 6 months Participants with non-CNSL presence of CNS or intraocular lymphoma lesions. CNSL participants with systemic presence of lymphoma, unable to complete lumbar puncture, under systemic corticosteroids at a dose > 8 mg/day (dexamethasone equivalent dose) within 14 days or requiring immunosuppressive or biologic therapy. Participants with infectious disease: Clinically significant cardiac disorders or abnormalities Another malignancy within 5 years prior to enrollment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer. Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption Women who are breast feeding Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DZD8586<br> | Drug: DZD8586<br>* DZD8586 treatment starting from 50 mg once daily. If tolerated, subsequent cohorts will test increasing doses of DZD8586.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Incidence of adverse events |  | 30 days after the last dose, assessed up to 2 years | 
| Part B: Objective Response Rate assessed by investigators |  | assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Objective Response Rate assessed by investigators |  | assessed up to 2 years | 
| Part A: Plasma and CSF concentration of DZD8586 |  | through discontinuation of treatment up to 10 weeks | 
| Part B: Duration of Response assessed by investigators |  | from date of first documented response until the date of documented progression, assessed up to 2 years | 
| Part B: Incidence of adverse events |  | 30 days after the last dose, assessed up to 2 years | 
| Part B: Plasma and CSF concentration of DZD8586 |  | through discontinuation of treatment, assessed up to 2 years |