A Phase Ⅰa/Ⅰb, Open-Label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Preliminary Efficacy of BC2027 in Patients With Advanced Solid Malignancies
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Incidence of dose limiting toxicities (DLTs)
Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Provide written informed consent.
- •Be at least 18 years old.
- •Have an Eastern Cooperative Group (ECOG) performance status (PS) of 0 or
- •Have a life-expectancy of at least 3 months based on the Investigator's assessment.
- •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.
- •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).
- •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.
- •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).
Exclusion Criteria
- •Patients who meet any of the exclusion criteria must not be enrolled in the study.
- •Prior treatment with GPC3-targeted ADC.
- •Prior treatment with systemic anticancer treatment, including investigational agents, within a period that is less than five half-lives or 2 weeks before the start of treatment, whichever is shorter.
- •Known hypersensitivity or delayed hypersensitivity reactions to the same class and/or any component of BC
- •Treatment with strong CYP3A4 inhibitors or inducers, and P-gp inhibitors within 14 days or 5 half-lives whichever is shorter, before the first dose.
- •For patients with advanced NSCLC:
- •a. Positive for driver oncogenes: including EGFR mutation, ALK gene fusion, ROS1 gene fusion, KRAS-G12C mutation, c-MET (exon 14 skipping, MET amplification and overexpression), HER2 mutation, RET gene fusion, etc.
- •For HCC patients:
- •Received local hepatic therapy including, but not limited to, surgery, radiotherapy, hepatic arterial embolization (TAE), hepatic arterial chemoembolization (TACE), hepatic arterial perfusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection) within 4 weeks prior to initiation of the study drug.
- •History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc if used for purposes of hepatic encephalopathy)
Arms & Interventions
BC2027 treatment group
BC2027 is administered via IV infusion, with 2 phases:
- Phase Ia (dose escalation): 4 levels (0.8/1.2/1.8/2.4 mg/kg); first 3 levels: Q2W (28-day cycle); 4th level: simultaneous exploration of Q2W (28-day cycle) and Q3W (21-day cycle).
- Phase Ib (dose expansion): 3 GPC3-positive cohorts (NSCLC/HCC/others) treated at Phase Ia's recommended dose.
Intervention: BC2027 for Injection (Drug)
Outcomes
Primary Outcomes
Incidence of dose limiting toxicities (DLTs)
Time Frame: 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
Time Frame: 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
Time Frame: Through study completion, an average of 2 years.
To assess the preliminary antitumor activity of BC2027 in patients with advanced solid malignancies
Secondary Outcomes
No secondary outcomes reported