A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of INV-9956 in Adult Patients With Advanced Metastatic Castration Resistant Prostate Cancer
- Conditions
- Advanced Metastatic Castration Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT06609005
- Lead Sponsor
- Shenzhen Ionova Life Sciences Co., Ltd.
- Brief Summary
This is a Phase 1 and Phase 2 study to determine the safety profile, RDR and/or MTD, DLT, PK/PD, and preliminary antitumor activity of INV-9956 in adult patients with advanced mCRPC.
- Detailed Description
This is a Phase 1 and Phase 2 study to determine the safety profile, RDR and/or MTD, DLT, PK/PD, and preliminary antitumor activity of INV-9956 in adult patients with advanced mCRPC.
The entire study consists of two parts: Phase 1 for dose escalation and Phase 2 for dose expansion. The screening period for all phases is up to 28 days, and one treatment cycle is 28 days.
The investigational drug will be co-administered with once daily (QD) dexamethasone 1.5 mg and fludrocortisone acetate 0.1 mg as corticosteroid replacement therapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 84
- Written informed consent obtained.
- Male aged ≥ 18 years.
- Histologically confirmed adenocarcinoma of the prostate.
- Castration resistant prostate cancer with serum testosterone <50 ng/dL.
- Metastatic disease.
- Ongoing androgen deprivation therapy with GnRH analogue or antagonist, or have had bilateral orchiectomy.
- Received at least one prior line of taxane-based chemotherapy and at least one line of hormonal AR targeted therapy (eg, abiraterone, enzalutamide). Patients who have refused or were intolerant to taxane-based chemotherapy may be enrolled.
- ECOG performance status 0-1.
- Adequate marrow, liver and kidney function.
- INR ≤1.5.
- Able to swallow study treatment.
- Has a life expectancy of > 3 months.
- Have a medical condition such as Crohn's disease or have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption.
- History of pituitary or adrenal dysfunction.
- Poorly controlled diabetes mellitus.
- Clinically significant abnormality in serum potassium and sodium.
- Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
- Active or unstable cardio-/cerebro-vascular disease, including thromboembolic events.
- History of congestive heart failure; cardiac disease, myocardial infarction within 6 months prior to enrollment.
- Prolonged QTcF interval.
- Active infection or other medical condition that would make corticosteroid contraindicated.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 INV-9956 Dose escalation Dose level 1 INV-9956 INV-9956 Dose escalation Dose level 1 is co-administered with dexamethasone and fludrocortisone acetate Phase 1 INV-9956 Dose escalation Dose level 2 INV-9956 INV-9956 Dose escalation Dose level 2 is co-administered with dexamethasone and fludrocortisone acetate Phase 1 INV-9956 Dose escalation Dose level 3 INV-9956 INV-9956 Dose escalation Dose level 3 is co-administered with dexamethasone and fludrocortisone acetate Phase 2 INV-9956 Dose expansion - Cohort A INV-9956 INV-9956 is co-administered with dexamethasone and fludrocortisone acetate Phase 2 INV-9956 Dose expansion - Cohort B INV-9956 INV-9956 is co-administered with dexamethasone and fludrocortisone acetate Phase 1 INV-9956 Dose escalation beyond the optimal dose - Dose level 4 INV-9956 INV-9956 Dose escalation Dose level 4 is co-administered with dexamethasone and fludrocortisone acetate Phase 1 INV-9956 Dose escalation beyond the optimal dose - Dose level 5 INV-9956 INV-9956 Dose escalation Dose level 5 is co-administered with dexamethasone and fludrocortisone acetate Phase 1 INV-9956 Dose escalation beyond the optimal dose - Dose level 6 INV-9956 INV-9956 Dose escalation Dose level 6 is co-administered with dexamethasone and fludrocortisone acetate
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) Within first 28 days of treatment The highest dose level at which at least 6 patients have been treated and less than 33% of patients experienced a DLT.
Recommended dose range (RDR) 12 months The RDR will be determined based on the PK and PD data, the preliminary clinical activity of INV-9956, as well as the incidence rate and nature of the toxicities observed in subsequent cycles beyond Cycle 1
- Secondary Outcome Measures
Name Time Method Characterize the safety of INV-9956 as assessed by CTCAE v5.0 12 months To analyze the safety profile of INV-9956 as a single agent by AE, clinical lab test results, ECG and Vital signs changes
Determine the PK using AUC of INV-9956 12 months To determine the pharmacokinetics (PK) using AUC of INV-9956 after a single dose and at steady state after multiple doses
Determine the PK using Cmax of INV-9956 12 months To determine the pharmacokinetics (PK) using Cmax of INV-9956 after a single dose and at steady state after multiple doses
Determine the blood concentration of steroid hormone 12 months To determine the blood concentration of steroid hormones at various timepoints as PD markers for INV 9956
Evaluate Radiographic progression-free survival (rPFS) 12 months To evaluate rPFS per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases)
Evaluate overall response rate (ORR) 12 months To evaluate ORR per PCWG-modified RECIST v1.1 (soft tissue response) and PCWG3 criteria (bone metastases)
Trial Locations
- Locations (17)
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
He'nan Cancer Hospital
🇨🇳Zhengzhou, He'nan, China
Hu'nan Cancer Hospital
🇨🇳Changsha, Hu'nan, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, Jiangsu, China
Liaoning Cancer Hospital
🇨🇳Shenyang, Liaoning, China
Shandong Cancer Hospital
🇨🇳Ji'nan, Shandong, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin Municipality, China
The First Affiliated Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Honor Health
🇺🇸Scottsdale, Arizona, United States
Scroll for more (7 remaining)The First Affiliated Hospital of Fujian Medical University🇨🇳Fuzhou, Fujian, ChinaNing XuPrincipal Investigator