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

Phase 1

Terminated

• Conditions: Metastatic Castration Resistant Prostate Cancer
• Interventions: Drug: DZD2269

• Registration Number: NCT04634344
• Lead Sponsor: Dizal Pharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-11-02
• Study First Submitted QC: 2020-11-12
• Study First Posted: 2020-11-18
• Study Start: 2021-04-12
• Primary Completion: 2022-05-05
• Study Completion: 2022-05-05
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-06
• Last Update Posted: 2022-07-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 16

Inclusion Criteria

1. Informed consent form, taken prior to any study specific procedures, sampling and/or analyses.
2. Male patients age ≥ 18 years (≥ 19 in S. Korea), ECOG status 0-1, Predicted life expectancy ≥ 12 weeks,
3. 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.
4. Be willing to provide blood samples and paired tumor tissue (if accessible) for the exploratory biomarker research
5. Total testosterone < 50 ng/dL at screening (except for subjects with prior orchiectomy, where testosterone does not need to be measured).
6. Adequate bone marrow reserve and organ system functions
7. LVEF ≥ 55% assessed by ECHO or MUGA

Exclusion Criteria

1. Cytotoxic chemotherapy from a previous treatment regimen within 21 days of the first dose of study treatment.
2. 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.
3. Prior exposure to therapeutic anticancer vaccines
4. 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
5. Prior/concomitant therapy with any other A2aR antagonist.
6. Live vaccines within 28 days prior to first dose.
7. Radiotherapy with a limited field for palliation within 1 week of the first dose of study treatment.
8. 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
9. Any unresolved toxicities > Grade 1 (except alopecia).
10. Bone pain due to metastatic bone disease that cannot be managed with a routine, stable dose of a narcotic analgesic
11. Active infections as outlined in protocol
12. Spinal cord compression.
13. Patients who require systemic use of corticosteroids (at any dose)
14. Refractory nausea and vomiting if not controlled by supportive therapy
15. Cardiac criteria as outlined in protocol
16. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DZD2269 as monotherapy	DZD2269	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea - Seoul St. Marys Hospital; 🇰🇷 Seoul, Korea, Republic of