Advanced Solid Malignancies
Conditions
Brief summary
This is a phase Ia/Ib, open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, and preliminary anticancer activity of BC2027 in patients with advanced solid Malignanciesr
Detailed description
This is a phase Ia/Ib, open-label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, and preliminary anticancer activity of BC2027 in patients with advanced solid Malignanciesr. This study will consist of two parts: Part 1, a dose escalation part (Phase Ia) and Part 2, a dose expansion part (Phase Ib). Both parts will include a screening period (within 28 days prior to dosing), a treatment period (Q2W(28-day cycle), Q3W(21-day cycle)), a safety follow-up period (45 days (±5 days) after last dose), and a survival follow-up period (every 12 weeks until death)
Interventions
DRUGBC2027 for Injection
Drug: BC2027 for Injection (lyophilized powder, 20 mg/vial) Administration: Administered via intravenous (IV) infusion, with dosing and frequency determined according to Phase Ia (dose escalation) and Phase Ib (dose expansion) study design.
Sponsors
Biocity Biopharmaceutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent. 2. Be at least 18 years old. 3. Have an Eastern Cooperative Group (ECOG) performance status (PS) of 0 or 1. 4. Have a life-expectancy of at least 3 months based on the Investigator's assessment. 5. Patients with advanced solid tumors confirmed by histology or cytology, who have failed standard therapy, have no available standard therapy, or are intolerant to standard therapy. 6. Phase 1a (dose escalation, Part 1) a. Have an advanced solid malignancy confirmed by histologic or cytologic examination that is known to express GPC3 including, but not limited to, HCC, NSCLC (particularly squamous cell NSCLC), sarcoma (undifferentiated), ovarian clear cell adenocarcinoma (OCCC), esophageal squamous cell carcinoma (ESCC). 7. Must provide either a previously archived tumor tissue sample or a fresh core or excisional biopsy from a site that was not irradiated. There must be at least 3-5 unstained sections. A formalin-fixed, paraffin-embedded (FFPE) tissue block is preferred to slides, and fresh biopsies are preferred over archival tissue. If archival tissue cannot be provided and a fresh biopsy cannot be obtained in Part 1, an exemption may be provided by the Sponsor. 8. Must have adequate organ function within 7 days prior to the start of study treatment as defined below: Hematological\* ANC ≥1,500/μL or ≥1.5×109/L Platelets ≥100,000/μL or ≥100×109/L (For HCC patients, PLTs ≥75×109/L) Hemoglobin ≥9.0 g/dL Kidney Function Creatinine clearance (CrCl)\*\* ≥50 mL/min Liver Function Total Bilirubin (TBIL) ≤1.5×ULN, or direct bilirubin ≤ULN (patients with total bilirubin level \>1.5×ULN). AST (SGOT) and ALT (SGPT) ≤2.5×ULN (≤5×ULN in patients with liver metastases) Coagulation International Normalized Ratio (INR), Prothrombin Time (PT), and activated partial thromboplastin time (aPTT) :INR≤1.5; PT and aPTT ≤1.5×ULN or within a therapeutic range if on an anticoagulant. \* Blood transfusion or growth factor support is not allowed within 14 days prior to blood sampling. \*\* CrCl should be calculated according to institutional standards. 9. Must have at least one measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (In the dose escalation part of the study (Part 1), patients without measurable lesions may be enrolled if they have evaluable disease and are approved by the sponsor). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 10. Must agree to use highly effective contraceptive measures if patient is a man or woman of childbearing potential. Highly effective contraceptive measures include measures like hormonal contraceptives, intrauterine devices, vasectomy, or tubal ligation, and others (Section 5.3), from the time of signing the informed consent until 6 months after the last dose of the study drug. Women of childbearing potential (WCBP) must have a negative blood or urine pregnancy test within 7 days prior to the first dose of study drug. Female patients with surgically sterile or are postmenopausal for at least 12 months without an alternative medical cause are also allowed. Additional Inclusion Criteria for Part 2 In addition to fulfilling the inclusion for Part 1, patients enrolling in cohorts in Part 2/Phase Ib must have: 1. Cohort 1 (NSCLC Cohort) 1. Positive expression of GPC3 confirmed by immunohistochemistry (IHC) assay, or with existing prior IHC test report documenting GPC3 positivity. 2. Patients with non-small cell lung cancer (NSCLC) who have failed no more than 3 prior lines of systemic antineoplastic therapy. 2. Cohort 2 (HCC Cohort) 1. IHC evidence of GPC3 expression on archival tumor or a fresh biopsy unless biopsy is not feasible or safe and with approval of the Sponsor. 2. The subject has received treatment with 1 prior regimen in the first line advanced setting consisting of an appropriate monoclonal antibody (mAb) targeting PD-1 or PD-L1 with an appropriate mAb targeting CTLA-4 and/or an appropriate tyrosine kinase inhibitor (TKI) or mAb targeting vascular endothelial growth factor (VEGF, e.g., bevacizumab). The subject must have progressed, demonstrated intolerance, or refused such treatment. If a subject had refused treatment, the reasons for such must be documented in the records and case report form (CRF). 3. The patient must have Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC (See Appendix 1), not amenable to locoregional therapy or refractory to locoregional therapy likely to result in reasonable clinical benefit, and not amenable to a curative treatment approach. 4. The subject has a Child-Pugh A score (See Appendix 2) within 7 days of study drug treatment. 3. Cohort 3 (Advanced GPC3 expressing solid cancer). 1. GPC3 positivity confirmed by IHC assay, or documented in prior IHC reports. 2. Patients excluding Cohort 1 and Cohort 2 with failure of ≤ 2 prior lines of systemic antineoplastic therapy.
Exclusion criteria
Patients who meet any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicities (DLTs) | Dose limiting toxicities (DLT) will be assessed At the end of Cycle 1 (each cycle is 28 or 21 days). | The incidence of dose-limiting toxicity (DLT) at different doses of BC2027 in patients with advanced solid malignancies |
| The safety and tolerability | Through study completion, an average of 2 years. | To assess the safety and tolerability of BC2027 in patients with advanced solid malignancies |
| Preliminary antitumor activity | Through study completion, an average of 2 years. | To assess the preliminary antitumor activity of BC2027 in patients with advanced solid malignancies |
Countries
China
Contacts
CONTACTFeng Liu
Outcome results
None listed