A First-in-Human, Open-label, Phase 1/2 Study of BOS-342 in Patients with Hepatocellular Carcinoma (HCC) and other Glypican 3 (GPC3)-expressing Tumors
- Conditions
- Hepatocellular Carcinoma (HCC)Other GPC3-expressing TumorsCancer - Liver
- Registration Number
- ACTRN12623000798662
- Lead Sponsor
- Boston Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 81
Age
1. Patients must be greater than or equal to 18 years, at the time of signing the informed consent.
Disease Characteristics
2. Histologically confirmed diagnosis of locally advanced, unresectable or metastatic HCC for which no standard curative therapy is available, or ineligible to accept/unable to tolerate standard therapy.
3. At least 1 unidimensional radiographically measurable lesion based on RECIST 1.1.
4. Availability of tumor biopsy:
• Phase 1 only: availability of a fresh biopsy or archival tumor samples no older than 2 years prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
• Phase 2 only: availability of fresh tumor biopsy, or an archival tumor sample taken after the last anticancer treatment and prior to the first study drug administration. Tumor biopsies and tumor archival material must be suitable for biomarker assessment (at least 10 slides). Patients who do not have adequate archival tissue will require a biopsy during the screening period. Refer to the Laboratory Manual for further information.
5. GPC3 Expression:
• Tumor samples are positive for GPC3 by local or central immunohistochemistry testing
Organ Function and Performance Score within 10 days of treatment initiation
6. Karnofsky score greater than or equal to 50.
7. Adequate renal function as defined by an estimated creatinine clearance of greater than or equal to 60 mL/min/1.73 m2 according to the Cockcroft-Gault equation.
8. Adequate hepatic function defined as:
• total bilirubin less than or equal to 1.5 × upper limit of normal (ULN) or normal conjugated bilirubin.
• aspartate aminotransferase [AST] and alanine aminotransferase [ALT] less than or equal to 3 × ULN, or less than or equal to 5 × ULN if due to liver involvement by tumor.
9. Adequate bone marrow function defined as:
• absolute neutrophil count greater than or equal to 1..5 × 109 cells/L.
• hemoglobin greater than or equal to 9.0 g/dL.
• platelets greater than or equal to 75 × 109 cells/L.
10. Adequate cardiac function defined as ejection fraction greater than 50% by echocardiogram, multigated acquisition (MUGA) or cardiovascular magnetic resonance imaging (MRI).
Pregnancy and Contraception
11. All patients must be willing and able to comply with a highly effective contraceptive method (Appendix 4) during and for 3 months after the treatment period. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Informed Consent
12. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol prior to initiation of any study procedures.
13. Willing and able to participate in the study and comply with all study requirements.
Cancer and Previous Cancer Therapy
1. Any persistent clinically significant greater than or equal to Grade 2 toxicity from prior cancer therapy except alopecia or sensory neuropathy or immunotherapy-related thyroid toxicity requiring replacement therapy.
2. Active CNS metastasis.
Exceptions: patients with stable brain metastases previously treated with surgery, radiotherapy or systemic therapy who are on a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, are eligible to enroll. CNS lesions that have been radiated should not be selected as target lesions for the purposes of RECIST evaluation.
3. Cancer directed therapy (chemotherapy, radiotherapy, biologic, immunotherapy, hormonal therapy or other) within the shorter of 28 days or 5 half-lives, if known, of the first dose of study drug.
Exception: palliative radiotherapy is allowed within 28 days prior to initiating treatment if associated toxicity resolved to less than or equal to Grade 1. However, lesions treated palliatively should not be selected as target lesions unless there has been clear progression of those lesions since the end of that treatment.
4. Prior or concurrent malignancy other than the malignancy under study, within the last 3 years.
Exception: Patients with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma or other malignancy for which there is very low risk of recurrence or progression are eligible.
Prior/Concomitant Therapy
5. Major surgery within 28 days prior to the first dose of study drug.
6. Systemic corticosteroid therapy or any other form of systemic immunosuppressive medication within 1 week prior to the first dose of study drug.
Exceptions: corticosteroid use as a premedication for IV contrast, transfusion therapy or prednisone less than or equal to 10 mg or equivalent per day for adrenal replacement or for patients with CNS disease, is permitted.
7. Live vaccine within 30 days prior to first day of treatment.
Infections
8. Active hepatitis B, defined as hepatitis B virus (HBV) surface antigen positive and HBV core antibody positive with positive HBV deoxyribonucleic acid (DNA), or HBV positive core antibody alone with positive HBV DNA, unless meeting all of the following criteria:
- Stable on antiviral therapy for hepatitis B virus (HBV) for at least 12 weeks.
- Adherence to antiviral therapy during study therapy per local standard of care.
- HBV viral load less than 200 IU / ml at screening
9. Active hepatitis C, defined as positive hepatitis C virus (HCV) antibody with positive HCV ribonucleic acid (RNA).
10. Known infection with human immunodeficiency virus (HIV), unless meeting all of the following criteria:
• Stable on antiretroviral therapy (ART) for at least 4 weeks.
• Adherence to ART during study therapy.
• HIV viral load of less than 400 copies/mL at Screening (or undetectable per local criteria).
• CD4 counts greater than or equal to 200/microliter.
11. Evidence or history of active or latent tuberculosis (TB) infection, defined as any 1 of the following:
• Current clinical, radiographical, or laboratory evidence of active TB.
• History of active TB.
• Positive QuantiFERON-TB Gold In-Tube or other diagnostic test in the absence of clinical manifestations.
12. Active uncontrolled infection being treated with systemic antibiotic, antiviral, or antifungal therapy.
Pregnancy and Breastfeeding
13. P
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method