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

NCT04634344 | Terminated Phase 1 FDA Drug

• 1 other identifier: DZ2019A0001
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 6

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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Drug concentrations of DZD2269 in plasma and urine

  to approximately 6 months

• Maximum plasma concentration (Cmax) of DZD2269

  up to approximately 6 months

• Area under the plasma concentration-time curve (AUC) of DZD2269

  up to approximately 6 months

• Objective Response Rate (ORR)

  Through the study completion, an average of around 1 year

• Disease Control Rate (DCR);

  Through the study completion, an average of around 1 year

Study Arms (1)

DZD2269 as monotherapy

EXPERIMENTAL

Drug: DZD2269

Interventions

DZD2269 DRUG

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.

DZD2269 as monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (6)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15215, United States

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea - Seoul St. Marys Hospital

Seoul, 06591, South Korea

Location

Related Publications (1)

• Bai Y, Zhang X, Zheng J, Liu Z, Yang Z, Zhang X. Overcoming high level adenosine-mediated immunosuppression by DZD2269, a potent and selective A2aR antagonist. J Exp Clin Cancer Res. 2022 Oct 14;41(1):302. doi: 10.1186/s13046-022-02511-1.

  PMID: 36229853 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 18, 2020
• Study Start: April 12, 2021
• Primary Completion: May 5, 2022
• Study Completion: May 5, 2022
• Last Updated: July 11, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); KR (4)