Clinical trial NCT06609005: A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of INV-9956 in Adult Patients With Advanced Metastatic Castration Resistant Prostate Cancer
Official title: A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Evidence of Antitumor Activity of INV-9956 in Adult Patients With Advanced Metastatic Castration Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Metastatic Castration Resistant Prostate Cancer
Keywords: mCRPC
Prostate Cancer
Lead sponsor: Shenzhen Ionova Life Sciences Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-09-23
Enrollment: 66
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1a, first-in-human, open-label dose-escalation study to determine the RDR and/or MTD, and to assess the DLT of INV-9956. The safety, tolerability, PK/PD, and preliminary antitumor activity of INV-9956 will be assessed in adult patients with advanced mCRPC.

Detailed description: This is a Phase 1a, first-in-human, open-label dose-escalation study to determine the RDR and/or MTD, and to assess the DLT of INV-9956. The safety, tolerability, PK/PD, and preliminary antitumor activity of INV-9956 will be assessed in adult patients with advanced mCRPC. The study will be conducted in 3 stages: Stage 1: dose escalation; Stage 2: dose expansion; Stage 3 (optional): Dose escalation beyond the optimal dose.

The total number of patients enrolled will depend upon the number of dose-escalation cohorts and the number of doses evaluated in Stage 2.

The investigational drug will be co-administered with dexamethasone and fludrocortisone acetate as corticosteroid replacement therapy.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained.
2. Male aged ≥ 18 years.
3. Histologically confirmed adenocarcinoma of the prostate.
4. Castration resistant prostate cancer with serum testosterone \<50 ng/dL.
5. Metastatic disease.
6. Ongoing androgen deprivation therapy with GnRH analogue or antagonist, or have had bilateral orchiectomy.
7. 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.
8. ECOG performance status 0-1.
9. Adequate marrow, liver and kidney function.
10. INR ≤1.5.
11. Able to swallow study treatment.
12. Has a life expectancy of \> 3 months.

Exclusion Criteria:

1. 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.
2. History of pituitary or adrenal dysfunction.
3. Poorly controlled diabetes mellitus.
4. Clinically significant abnormality in serum potassium and sodium.
5. 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.
6. Active or unstable cardio-/cerebro-vascular disease, including thromboembolic events.
7. History of congestive heart failure; cardiac disease, myocardial infarction within 6 months prior to enrollment.
8. Prolonged QTcF interval.
9. Active infection or other medical condition that would make corticosteroid contraindicated.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Within first 28 days of treatment
measure: Recommended dose range (RDR)
timeFrame: 12 months
Secondary outcomes:
measure: Characterize the safety of INV-9956 as assessed by CTCAE v5.0
timeFrame: 12 months
measure: Determine the PK using AUC of INV-9956
timeFrame: 12 months
measure: Determine the PK using Cmax of INV-9956
timeFrame: 12 months
measure: Determine the blood concentration of steroid hormone
timeFrame: 12 months
measure: Evaluate Radiographic progression-free survival (rPFS)
timeFrame: 12 months
measure: Evaluate overall response rate (ORR)
timeFrame: 12 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: Newport Beach
country: United States
facility: Hoag Family Cancer Institute
state: California
city: San Antonio
country: United States
facility: UT Health
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: