Clinical trial NCT04634344: Assess the Safety, Tolerability, PK and Anti-tumor Efficacy of DZD2269 in Patients With MCRPC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Castration Resistant Prostate Cancer
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-11-18
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of AEs and SAEs
timeFrame: From screening to 28 days after the last dose
measure: Incidence of DLTs
timeFrame: From the first dose of study treatment up to the last day of Cycle 1 (28 days after start of multiple dosing)
Secondary outcomes:
measure: Drug concentrations of DZD2269 in plasma and urine
timeFrame: to approximately 6 months
measure: Maximum plasma concentration (Cmax) of DZD2269
timeFrame: up to approximately 6 months
measure: Area under the plasma concentration-time curve (AUC) of DZD2269
timeFrame: up to approximately 6 months
measure: Objective Response Rate (ORR)
timeFrame: Through the study completion, an average of around 1 year
measure: Disease Control Rate (DCR);
timeFrame: Through the study completion, an average of around 1 year
measure: Duration of Response (DoR)
timeFrame: Through the study completion, an average of around 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Seoul St. Marys Hospital
Study officials:
References:
citation: 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.