Advanced Solid Tumors
Conditions
Interventions
Phase 1a Monotherapy Dose Escalation:BG-C477 intravenous infusion with dose escalation, starting at 1.5 mg/kg every 3 weeks
Phase 1a Monotherapy Safety Expansion:BG-C477 intravenous infusion at the safety dose level selected by SMC
Phase 1b Part A (Dose Optimization):BG-C477 intravenous infusion combined with capecitabine (with or without bevacizumab)
Phase 1b Part B (Combination Therapy Expansion):BG-C477 intravenous infusion combined with capecitabine (with or without bevacizumab)
Sponsors
Sun Yat-sen University Cancer Center (Sun Yat-sen University Cancer Hospital, Sun Yat-sen University Cancer Institute)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Patients must sign the ICF and be capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 2. Patients must be >= 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), inclusive, at the time of signing the informed consent. 3. Phase 1a (Monotherapy Dose Escalation and Safety Expansion): Patients with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, limited to CRC, GC/GEJC, NSCLC, SCLC or pancreatic cancer, who were previously treated with at least 2 lines of standard systemic therapy or for whom no standard treatment is available in the medical judgment of the investigator. Patients with molecular aberrations or a highly expressed tumor associated antigen for which an appropriate molecular targeted therapy exists, must be adequately treated with that therapy. (1) For CRC: Patients with known MSI-high/deficient mismatch repair status must have received at least one line of treatment with an immune checkpoint inhibitor if available as locally approved treatment. (2) For non-CRC: Patients should have a test result of serum CEA >= 5 ng/ml or documented tumor tissue CEA positivity by immunohistochemistry testing per local laboratory. Phase 1b (Dose Expansion): (1) Part A (Dose Optimization): Patients with histologically or cytologically confirmed advanced, metastatic, or unresectable CRC, GC/GEJC, or other selected tumor types as described in Section 4.1.1.6. Patients must have been previously treated with 1 or 2 lines of standard systemic therapy. For non-CRC, patients should have a test result of serum CEA >= 5 ng/ml or documented tumor tissue CEA positivity by immunohistochemistry testing per local laboratory. (2) Part B (Combination Therapy Expansion): Patients with histologically confirmed CRC who have only received 1 line of systemic therapy for the advanced, metastatic, or unresectable disease. 4. Patients must provide agreement for collection of archival tumor tissue (FFPE block or approximately 10-15 freshly cut unstained FFPE slides) for Phase 1a and Phase 1b. For Phase 1a Safety Expansion and Phase 1b cohorts, archival tumor tissues should be = 1 measurable lesion as assessed by RECIST v1.1. 6. Patients must have a stable ECOG Performance Status of = 1.5 × 10^9/L 2) Platelets >= 100 × 10^9/L 3) Hemoglobin >= 90 g/L (2) Creatinine clearance >= 60 mL/min, as determined by CKD-EPI equation (Appendix 7) (3) Serum total bilirubin = 2.0 g/dL (5) AST and ALT <= 2.5 × ULN or < 5 × ULN if hepatic metastases are pr
Exclusion criteria
Exclusion criteria: 1. Previous ADCs targeting CEA or ADCs containing TOP1 inhibitors as payloads. 2. History of severe allergic reactions, severe reaction to infusion, or hypersensitivity to the active ingredient and excipients of the study drug(s) or protein-based therapeutics. 3. Patients with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Patients with a history of treated and, at the time of screening, stable CNS metastases are eligible, provided they meet all the following criteria: (1) Show no evidence of interim progression during brain imaging at screening, and there is no evidence of new brain metastases. (2) Are clinically stable for >= 6 weeks. (3) Have measurable disease outside the CNS. (4) Have no ongoing requirement for corticosteroids as therapy for CNS disease, off corticosteroids for at least 2 weeks before the first dose of study drug(s); anticonvulsants at a stable dose are allowed. (5) Have no stereotactic radiation or whole-brain radiation 2 L/min by nasal cannula are excluded. 7. Clinically significant infections (including tuberculosis infection, etc) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy = 500 IU/mL (or >= 2500 copies/mL) at screening. Note: Inactive hepatitis B surface antigen carriers, with treated and stable hepatitis B (HBV DNA = 350 cells/µL at screening. (4) Have viral load of < 400 copies per mL before enrollment. (5) Have no opportunistic infection reported within 12 months before enrollment. (6) Are stable on antiretroviral therapy for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability for BG-C477 monotherapy in patients with selected advanced solid tumors. (Phase 1a);To determine RP2D of BG-C477 alone and in combination with capecitabine with or without bevacizumab(Phase 1b);To determine the MTD or MAD and RDFE[s] of BG-C477 monotherapy (Phase 1a);To assess the antitumor activity of BG-C477 alone and in combination with capecitabine with or without bevacizumab in patients with selected advanced solid tumors (Phase 1b); | — |
Secondary
| Measure | Time frame |
|---|---|
| To further assess the safety and tolerability of BG-C477 alone and in combination with capecitabine with or without bevacizumab (Phase 1b);To characterize the pharmacokinetics of BG-C477 monotherapy (Phase 1a);To further characterize the PK of BG-C477 alone and in combination with capecitabine with or without bevacizumab (Phase 1b);To further evaluate the antitumor activity of BG-C477 alone and in combination with capecitabine with or without bevacizumab (Phase 1b);To further assess the host immunogenicity to BG-C477 (Phase 1b);To assess the preliminary antitumor activity of BG-C477 monotherapy(Phase 1a);To assess host immunogenicity to BG-C477(Phase 1a); | — |
Countries
China
Contacts
Public ContactXu Ruihua
Sun Yat-sen University Cancer Center (Sun Yat-sen University Cancer Hospital, Sun Yat-sen University Cancer Institute)
Outcome results
None listed