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

NCT ID: NCT04634344

Last Updated: 2022-07-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-12
• Study Completion Date: 2022-05-05

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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DZD2269 as monotherapy

Group Type: EXPERIMENTAL

DZD2269

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Dizal Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Severance Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea - Seoul St. Marys Hospital

Seoul, , South Korea

Countries

United States; South Korea

References

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.

Reference Type: DERIVED

PMID: 36229853 (View on PubMed)

Other Identifiers

DZ2019A0001

Identifier Type: -

Identifier Source: org_study_id