A Study of HB0045 Injection in Patients With Advanced Solid Tumors

Inclusion Criteria

• •1. Male or female, aged ≥ 18 years.
• •2. The subject can understand and willing to sign the ICF and is willing and able to comply with all study procedures.
• •3. Phase I: Patients with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors (or clinically diagnosed hepatocellular carcinoma) that failed (progressed on or are intolerant of) all standard therapies known to provide clinical benefit; \[These solid tumors include but not limited to: pancreatic, colorectal, ovarian, breast, lung, head and neck, prostate, renal cancer, and sarcoma, etc.\]
• •4. Phase II: Patients who have had at least one systemic therapy and has progressed, and might benefit from the study drug in the Investigator's judgment, and have the following histological types (The types of tumors and the number of treatment lines may be adjusted based on phase I results and /or SRC discussions):
• •a) Pancreatic cancer cohort: i. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma. ii. Unresectable, locally advanced recurrent or metastatic. b) CRC cohort: i. Histologically or cytologically confirmed colorectal cancer. ii. Molecular typing: non-dMMR/ non-MSI-H colorectal cancer. c) Ovarian cancer cohort: i. Histologically or cytologically confirmed unresectable metastatic ovarian, fallopian tube or peritoneal cancer ii. Epithelial type including high-grade serous cell carcinoma, endometrioid carcinoma or clear cell carcinoma.
• •iii. No history of ileus (including signs or symptoms of ileus) within 3 months prior to screening.
• •iv. Patients who had not received enterostomy within 3 months prior to screening.
• •v. Have failed (progressed on or are intolerant of) all standard therapies known to provide clinical benefit; including but not limited to treatment with platinum-based chemotherapy if platinum-sensitive disease, and treatment with chemotherapy + bevacizumab if platinum-resistant and have not received prior bevacizumab.
• •d) Other advanced cancer cohort(s): Tumor specific type that demonstrated partial response to HB0045 in dose escalation phase.
• •5. At least one measurable lesion as per RECIST v. 1.1 defined as non-nodal lesions having at least one dimension with a minimum size of 10 mm in the longest diameter by CT or MRI scan or ≥15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 21 days prior to the first dose.
• •Note: Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• •6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• •7. Life expectancy ≥12 weeks.
• •8. Patients with active hepatitis B virus (HBV) without active disease (HBV DNA titer \<1000 cps/mL or 200 IU/mL), or who are cured of hepatitis C virus (HCV) with a negative HCV RNA test may be enrolled at the investigator's discretion.
• •9. Patients with known human immunodeficiency virus (HIV) infection and a cluster of differentiation 4 (CD4) count that is documented to be ≥350 cells/mm3 within 12 months before study screening, and if HIV-infected patients with a lower CD4+ count (\<350cell/ mm3)，should be eligible only if they have a potentially curable malignancy or for interventions in a later stage of development that have demonstrated prior activity with a given cancer.
• •10. Adequate organ function within 14 days of the first dose as defined by the following criteria:
• •1. Hematology i. absolute neutrophil count (ANC) ≥ 1.5×109/L ii. platelets (PLT) ≥ 100×109/L iii. hemoglobin (HGB) ≥ 90 g/L Note: The above items require that patients have not received any blood component or supportive therapy with growth hormones within two weeks prior to blood sampling.
• •2. Renal function: Calculated creatinine clearance (CrCL) \> 30 mL/min (Cockroft-Gault Equation)
• •3. Liver function i. AST and ALT ≤ 2.5×ULN; AST or ALT ≤ 5×ULN if liver metastases are present ii. Total bilirubin (TBIL) ≤ 1.5×ULN; ≤3 X ULN for patients with Gilbert's disease
• •4. Coagulation function i. International normalized ratio (INR) or prothrombin time (PT)≤ 1.5×ULN (unless the patient is on stable dose of oral anticoagulant) ii. Activated partial thromboplastin time (APTT)≤ 1.5×ULN
• •11. Women of childbearing potential must confirm a negative serum pregnancy test within 3 days prior to the initiation of study treatment and begin use of an effective birth control directly after testing negative for pregnancy; Fertile patients and their partners must agree to use acceptable contraception for the duration of study drug use and for 120 days after the last administration of study treatment.
• •Acceptable contraception Single method i. Intrauterine device (IUD) ii. Vasectomy of a female subject's male partner iii. Contraceptive rod implanted into the skin Combined method (requires the use of two of the following) i. Diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide) ii. Cervical cap with spermicide (nulliparous women only) iii. Contraceptive sponge (nulliparous women only) iv. Male condom or female condom (cannot be used together) v. Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin -only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection.
• •12. Recovery to Grade 0-1 from adverse events (AEs) related to prior anticancer therapy except alopecia, \< Grade 2 sensory neuropathy, and endocrinopathies controlled with hormone replacement therapy.