Assess the Safety, Tolerability, PK and Anti-tumor Efficacy of DZD2269 in Patients With MCRPC

Study Overview
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Brief Summary
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This study will treat patients with Metastatic Castration Resistant Prostate Cancer who have progressed following prior therapy. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy.

Detailed Description
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A first-time-in-human, Phase I, open-label, multicenter study to determine safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of DZD2269 in patients with mCRPC.

Official Title
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A Phase I, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD2269 in Patients With Metastatic Castration Resistant Prostate Cancer

Conditions
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Metastatic Castration Resistant Prostate Cancer

Intervention / Treatment
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* Drug: DZD2269


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form, taken prior to any study specific procedures, sampling and/or analyses. Male patients age ≥ 18 years (≥ 19 in S. Korea), ECOG status 0-1, Predicted life expectancy ≥ 12 weeks, All patients enrolled must have histologically confirmed diagnosis of adenocarcinoma of the prostate, with metastatic disease, and must also previously progressed on standard-of-care (SoC) therapy (i.e., abiraterone or enzalutamide, taxanes such as docetaxel or cabazitaxel) despite castrate levels of testosterone. Be willing to provide blood samples and paired tumor tissue (if accessible) for the exploratory biomarker research Total testosterone < 50 ng/dL at screening (except for subjects with prior orchiectomy, where testosterone does not need to be measured). Adequate bone marrow reserve and organ system functions LVEF ≥ 55% assessed by ECHO or MUGA Exclusion Criteria: Cytotoxic chemotherapy from a previous treatment regimen within 21 days of the first dose of study treatment. Major surgery procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study. Prior exposure to therapeutic anticancer vaccines Prior immune-mediated therapy including, but not be limited to, anti-CTLA-4, anti-PD1, anti-PDL1 and anti-PDL2 must have a wash-out period of ≥ 30 days before dosing Prior/concomitant therapy with any other A2aR antagonist. Live vaccines within 28 days prior to first dose. Radiotherapy with a limited field for palliation within 1 week of the first dose of study treatment. Patients currently receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4, sensitive CYP3A4 substrates with narrow therapeutic index, and sensitive MATE1 and MATE2-K substrates with narrow therapeutic range Any unresolved toxicities > Grade 1 (except alopecia). Bone pain due to metastatic bone disease that cannot be managed with a routine, stable dose of a narcotic analgesic Active infections as outlined in protocol Spinal cord compression. Patients who require systemic use of corticosteroids (at any dose) Refractory nausea and vomiting if not controlled by supportive therapy Cardiac criteria as outlined in protocol Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer or other cancer from which the patient has been disease free for ≥ 2 years or which will not limit survival to < 2 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DZD2269 as monotherapy<br> | Drug: DZD2269<br>* A single dose of DZD2269 starting at 5 mg will be given on Cycle 0 and then followed by a wash-out period. Multiple doses of DZD2269 at the same dose level will be given once daily after the wash-out period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs and SAEs | To investigate the safety and tolerability of DZD2269 as monotherapy in patients with metastatic castration resistant prostate cancer (mCRPC) | From screening to 28 days after the last dose | 
| Incidence of DLTs | To establish Maximum Tolerated Dose (MTD) (if possible) in patients with mCRPC | From the first dose of study treatment up to the last day of Cycle 1 (28 days after start of multiple dosing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug concentrations of DZD2269 in plasma and urine | Pharmacokinetics endpoints | to approximately 6 months | 
| Maximum plasma concentration (Cmax) of DZD2269 | Pharmacokinetics endpoints | up to approximately 6 months | 
| Area under the plasma concentration-time curve (AUC) of DZD2269 | Pharmacokinetics endpoints | up to approximately 6 months | 
| Objective Response Rate (ORR) | To assess the preliminary anti-tumor efficacy of DZD2269 as monotherapy based on modified RECIST | Through the study completion, an average of around 1 year | 
| Disease Control Rate (DCR); | To assess the preliminary anti-tumor efficacy of DZD2269 as monotherapy based on modified RECIST | Through the study completion, an average of around 1 year | 
| Duration of Response (DoR) | To assess the preliminary anti-tumor efficacy of DZD2269 as monotherapy based on modified RECIST | Through the study completion, an average of around 1 year |