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

Metastatic Castration Resistant Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04634344
• Other study ID #: DZ2019A0001
• Status: Terminated
• Phase: Phase 1
• Start date: April 12, 2021
• Est. completion date: May 5, 2022

Study information

• Verified date: July 2022
• Source: Dizal Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: May 5, 2022
• Est. primary completion date: May 5, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea - Seoul St. Marys Hospital	Seoul
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Dizal Pharmaceuticals

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Drug concentrations of DZD2269 in plasma and urine	Pharmacokinetics endpoints	to approximately 6 months
Secondary	Maximum plasma concentration (Cmax) of DZD2269	Pharmacokinetics endpoints	up to approximately 6 months
Secondary	Area under the plasma concentration-time curve (AUC) of DZD2269	Pharmacokinetics endpoints	up to approximately 6 months
Secondary	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
Secondary	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
Secondary	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