Prostate Cancer
Conditions
Brief summary
A Phase I Clinical Study of GLR2037 in Patients with Advanced Prostate Cancer
Interventions
DRUGGLR2037
GLR2037 administered QD for 28 day cycles.
Sponsors
Gan & Lee Pharmaceuticals.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male, aged ≥ 18 years. 2. Histologically or cytologically confirmed adenocarcinoma of the prostate, without neuroendocrine or small cell features. 3. Metastatic bone or soft tissue lesions documented by imaging. 4. Prior surgical or medical castration. 5. Castrate level of testosterone at screening (≤ 50 ng/dL or 1.73 nmol/L). 6. Phase Ia and Ib: Prior treatment with at least one novel endocrine therapy (e.g., abiraterone, enzalutamide, apalutamide, darolutamide, rezlutamide, etc.); patients in the dose-escalation phase of Phase Ia must have received at least one prior line of chemotherapy (e.g., docetaxel, cabazitaxel, etc.). 7. Evidence of disease progression during castration therapy in patients with metastatic prostate cancer at screening. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 9. Adequate organ function meeting protocol-specified criteria. 10. Life expectancy ≥ 3 months. 11. Fertile male subjects and their partners must agree to use effective contraception (e.g., condoms) and refrain from donating sperm from the first dose of the study drug until 3 months after the last dose. 12. Willing to participate in this clinical trial, understand the study procedures, and have signed the informed consent form.
Exclusion criteria
"1. Prior use of AR protein degraders. 2. Use of any other biological and/or immunological anti-tumor therapy (except castration therapy), targeted therapy, estrogen therapy, anti-androgen therapy, or other interventional investigational drug therapy; or receipt of systemic chemotherapy, systemic radiotherapy, or Chinese herbal/patent medicine with anti-tumor indications (as clearly stated in the package insert) within 4 weeks (or 5 half-lives, whichever is shorter) prior to the first dose; or receipt of nitrosoureas, bicalutamide, or nilutamide within 6 weeks (or 5 half-lives, whichever is shorter) prior to the first dose. 3\. Subjects who have used bisphosphonates or RANKL inhibitors for the treatment of bone metastases or bone-related diseases within 2 weeks prior to the first dose. 4\. Have received systemic immunosuppressive therapy within 2 weeks prior to the first dose. 5\. Use of strong inhibitors or inducers of CYP2C9 or CYP3A4 within 14 days or 5 half-lives (whichever is longer) prior to the first dose. 6\. Patients with imaging evidence of brain or central nervous system metastases. 7\. Severe bone injury caused by bone metastases of prostate cancer as judged by the investigator. 8\. Concurrent uncontrolled hypertension at screening. 9. Presence of active cardiac disease or occurrence of arterial or venous thromboembolism within 6 months prior to the first dose. 10\. History of other malignancies within 5 years prior to the first dose. 11. Have active hepatitis B (HBsAg positive and HBV-DNA titer ≥ 1×10³ copies/mL), hepatitis C (HCV antibody positive); or severe infections requiring antibiotics, antiviral or antifungal drugs for control. 12.History of immunodeficiency or organ transplantation. 13.Concurrent dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting drug administration and absorption. 14.Not recovered from adverse events of prior anti-tumor therapy to ≤ Grade 1 at screening. 15.Known allergy to any component or excipient of GLR2037. 16.Subjects who have received palliative radiotherapy or major surgery (Grade 3-4) within 4 weeks prior to the first dose, or have participated in other drug clinical trials within 4 weeks prior to the first dose. 17.Plan to receive any other anti-tumor therapy during the study treatment period other than those specified in the protocol. 18.Any concomitant disease or other condition that, in the judgment of the investigator, poses a serious risk to the safety of the subject or could affect the subject's completion of the study. "
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with Adverse Events as a measure of safety and tolerability of GLR2037 | From signing of informed consent to 30 days after last dose (safety follow-up) | Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 6.0), timing, seriousness, and relationship to study drug. |
| Incidence of DLT of GLR2037 | 28 Days | First Cycle Dose limiting toxicities characterized by type, frequency, severity(as graded by NCI CTCAE version 6.0), timing, seriousness, and relationship to study drug |
| Incidence of laboratory abnormalities as a measure of safety and tolerability of GLR2037 | From signing of informed consent to 30 days after last dose (safety follow-up) | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of pharmacokinetic (PK) parameter area under the concentration-time curve (AUC). | At predefined intervals throughout the GLR2037 treatment period, up to last dose of GLR2037 | Concentration-time curve (AUC) for single dose of GLR2037 PK parameters will be assessed when applicable after a single dose and after multiple doses. |
| Assessment of pharmacokinetic parameter maximum concentration (Cmax). | At predefined intervals throughout the GLR2037 treatment period, up to last dose of GLR2037 | Maximum concentration (Cmax) for single and multiple dose of GLR2037 PK parameters will be assessed when applicable after a single dose and after multiple doses. |
| Assessment of pharmacokinetic parameter time to maximum concentration (Tmax) | At predefined intervals throughout the GLR2037 treatment period, up to last dose of GLR2037 | Time to maximum concentration (Tmax) for single and multiple dose of GLR2037 PK parameters will be assessed when applicable after a single dose and after multiple doses. |
| To evaluate the clinical anti-tumor activity of GLR2037 in patients with mCRPC | 12 Weeks | Evaluate PSA in patients in both dose groups |
Countries
China
Contacts
CONTACTYunda Zhuge
Outcome results
None listed