This Study is to Evaluate OBI-3424 Safe and Effective Treatment Dose in Subjects With Hepatocellular Carcinoma or Castrate Resistant Prostate Cancer

• Status: Recruiting
• Trial end date: 2023-03-30
• Target enrollment: 0
• Participant gender: All

Summary

A first-in-human open-label, Phase I/II study to evaluate the safety, tolerability, MTD/RP2D, PK, and preliminary efficacy of OBI-3424 administered as a single agent in patients with solid tumors, hepatocellular carcinomas (HCC), and castrate-resistant prostate cancer (CRPC).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: OBI Pharma, Inc

Criteria

Inclusion Criteria:

1. At least 18 years of age

2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC)

3. Recovered from toxicities of prior therapy to Grade 0 or 1

4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) criteria or for rising prostate specific antigen (PSA) according to the Prostate Cancer Working Group 3 (PCWG3) criteria for subjects with CRPC

5. Available tissue (including archival tissue) for retrospective AKR1C3 expression analysis (except for subjects with CRPC where this is not a requirement for inclusion). Patients must agree to a fresh tumor biopsy in case an archival sample is not available.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Cardiac QTcF interval ≤ 450msec for males and ≤470 msec for females

8. Acceptable liver function:

1. Bilirubin ≤1.5 × institutional ULN

2. AST and ALT ≤3.0 × ULN, or ≤5.0 × ULN for subjects with liver involvement

9. Acceptable renal function:

a. Creatinine clearance >30 mL/min according to the Cockcroft-Gault formula

10. Acceptable hematologic status (without hematologic support, other than red blood cell transfusion):

1. ANC ≥1500 cells/μL

2. Platelet count ≥100,000/μL

3. Hemoglobin ≥9.0 g/dL

11. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation.

Dose Escalation Phase Subjects Only (Inclusion Criteria):

12. Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective

13. Tumor progression after most recent therapy

Expansion Phase- CRPC Cohort Only (Inclusion Criteria):

14. Histologically confirmed diagnosis of adenocarcinoma of the prostate

15. Documented evidence of metastatic CRPC

16. Progressive disease according to the PCWG3 criteria for rising PSA or according to RECIST version 1.1 for measurable soft tissue disease

17. Receipt of two or more lines of systemic standard of care treatment

18. Castrate due to prior bilateral orchiectomy or ongoing LHRH analog therapy (with or without an androgen synthesis inhibitor). Subject must be able to remain on androgen deprivation therapy during study treatment (if no prior orchiectomy)

19. Serum testosterone concentration of 50 ng/dL or less

Expansion Phase - CRPC Cohort Only (Inclusion Criteria):

20. Histologically confirmed advanced HCC not amenable to curative surgery or local treatment

21. Prior treatment with an FDA-approved systemic therapy, including but not limited to sorafenib, lenvatinib, regorafenib, and/or nivolumab. Subjects may have progressed on, been intolerant of, or refused treatment with these agents

22. Child-Pugh Classification with score ≤6 points within 7 days of the first study dose

23. No history of hepatic encephalopathy

24. No prior or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control (subjects who have ascites only on radiographic imaging are eligible)

25. No concomitant anticoagulation treatment

26. No active alcohol abuse

27. Adequate organ function for this HCC cohort is the same as for the Dose Escalation Cohort except as specified here (and if safety data from Dose Escalation allows):

1. Platelet count ≥60,000/μL (HCC subjects with platelet counts ≥60,000/μL to <99,000/μL must not have had hemorrhage within 6 months prior to study entry or, if esophageal varices are present, the subject must have been treated prior to study entry)

2. ANC ≥1000 cells/μL

3. Serum bilirubin ≤3 mg/dL

4. AST/ALT ≤5 × ULN,

5. International normalized ratio (INR) ≤2.3 or prothrombin time ≤6 seconds above control

6. Albumin ≥2.8 g/dL

Exclusion Criteria:

1. Prior radiotherapy to more than 25% of the bone marrow

2. Symptomatic brain metastases, unless previously treated and well controlled for at least 4 weeks after central nervous system (CNS)-directed treatment as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the Screening Period. Patients with known leptomeningeal disease are excluded.

3. Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the current study

4. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery

5. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

6. Treatment with radiation therapy, surgery, chemotherapy, targeted therapies or hormones within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C)

7. Concomitant use of strong CYP3A4 inhibitors/inducers

8. Subjects who participated in an investigational drug or device study within 28 days prior to study entry

9. Subjects with known HIV infection, unless CD4 ≥500 cells/μL and HIV RNA below the limit of detection on stable doses of antiretroviral therapy

10. Subjects with chronic HBV infection, unless Screening viral load <100 IU/mL on stable doses of antiviral therapy. Note: Subjects with chronic HCV infection are allowed to enroll in the study but do not have a defined maximum viral load requirement for study entry.

11. Females who are pregnant or breast-feeding

12. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

13. Unwillingness or inability to comply with the study protocol for any reason