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

• ClinicalTrials.gov Identifier: NCT04634344
• Recruitment Status: Recruiting
• First Posted: November 18, 2020
• Last Update Posted: October 27, 2021
• Sponsor: Dizal Pharmaceuticals
• Information provided by (Responsible Party): Dizal Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Castration Resistant Prostate Cancer	Drug: DZD2269	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 12, 2021
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Incidence of AEs and SAEs [ Time Frame: 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)
2. Incidence of DLTs [ Time Frame: 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 :

1. Drug concentrations of DZD2269 in plasma and urine [ Time Frame: to approximately 6 months ]
   Pharmacokinetics endpoints
2. Maximum plasma concentration (Cmax) of DZD2269 [ Time Frame: up to approximately 6 months ]
   Pharmacokinetics endpoints
3. Area under the plasma concentration-time curve (AUC) of DZD2269 [ Time Frame: up to approximately 6 months ]
   Pharmacokinetics endpoints
4. Objective Response Rate (ORR) [ Time Frame: 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
5. Disease Control Rate (DCR); [ Time Frame: 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
6. Duration of Response (DoR) [ Time Frame: 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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Ziyi Liu; +86 21 6109 5852; Ziyi.Liu@dizalpharma.com

Contact: Pamela Yang, M.D & Ph. D; +86 21 61097866; pamela.yang@dizalpharma.com

Locations

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

United States, Pennsylvania

University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15215

Korea, Republic of

Severance Hospital; Recruiting

Seoul, Korea, Republic of, 03722

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 05505

Contact: Lee

Samsung Medical Center; Recruiting

Seoul, Korea, Republic of, 06351

The Catholic University of Korea - Seoul St. Marys Hospital; Recruiting

Seoul, Korea, Republic of, 06591

Sponsors and Collaborators

Dizal Pharmaceuticals

More Information

• Responsible Party: Dizal Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04634344
• Other Study ID Numbers: DZ2019A0001
• First Posted: November 18, 2020
• Last Update Posted: October 27, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases