A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of INV-9956 in Adult Patients With Advanced Metastatic Castration Resistant Prostate Cancer

Shenzhen Ionova Life Sciences

Status and phase: Enrolling; Phase 1

Conditions: Advanced Metastatic Castration Resistant Prostate Cancer

Treatments: Drug: INV-9956

Study type: Interventional

Funder types: Industry

Identifiers

NCT06609005

INV-9956-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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66 participants in 8 patient groups

Stage 1 INV-9956 Dose escalation Dose level 1

Experimental group

Description:

INV-9956 Dose escalation Dose level 1 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 1 INV-9956 Dose escalation Dose level 2

Experimental group

Description:

INV-9956 Dose escalation Dose level 2 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 1 INV-9956 Dose escalation Dose level 3

Experimental group

Description:

INV-9956 Dose escalation Dose level 3 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 2 INV-9956 Dose expansion - Dose Level 1

Experimental group

Description:

INV-9956 Dose expansion Dose Level 1 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 2 INV-9956 Dose expansion - Dose Level 2

Experimental group

Description:

INV-9956 Dose expansion Dose Level 2 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 4

Experimental group

Description:

INV-9956 Dose escalation Dose level 4 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 5

Experimental group

Description:

INV-9956 Dose escalation Dose level 5 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956

Stage 3 INV-9956 Dose escalation beyond the optimal dose - Dose level 6

Experimental group

Description:

INV-9956 Dose escalation Dose level 6 is co-administered with dexamethasone and fludrocortisone acetate

Treatment:

Drug: INV-9956