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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: DZD2269

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea - Seoul St. Marys Hospital
• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15215
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DZD2269 as monotherapy	Drug: DZD2269; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dizal Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): May 5, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 12, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: DZ2019A0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No