Advanced Solid Tumor, Cervical Cancer
Conditions
Brief summary
It is a phase I/II open label, multicenter study to assess the safety, tolerability, pharmacokinetics, and efficacy of HB0028 in patients with advanced solid tumors.
Detailed description
This is a phase I/II, multicenter, open-label, first-in-human study in patients with advanced solid tumors. During the phase I study, the safety and tolerability of HB0028 will be evaluated in patients with advanced solid tumors. In the phase II study, the safety and efficacy of HB0028 at the RP2D will be evaluated in cohorts of patients with specific solid tumors.
Interventions
DRUGHB0028
Patients will be assigned to dose regimens in the order of enrollment, and they will receive their assigned fixed dose of HB0028 via intravenous infusion. HB0028 IV every 3 weeks (q3w).
Sponsors
Shanghai Huaota Biopharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A single-subject cohort will be enrolled at the protocol starting dose of HB0028 every 3 weeks (Q3W). Dose escalation will proceed to the next main dose level according to the 3+3 dose-escalation procedure until the MTD/OBD is reached. Phase II of the study will be initiated at the Sponsor's discretion at the dose level and treatment schedule which was established as the recommended Phase 2 dose (RP2D) in the dose-escalation phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet all the following criteria to be eligible for participation in this study: 1. Male or female. Age ≥ 18 years. 2. The subject is able to understand and willing to sign the Informed Consent Form(ICF); willing and able to comply with all study procedures. 3. a) dose escalation: Patients with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors (or clinically diagnosed hepatocellular carcinoma) that failed all standard therapies known to provide clinical benefit; \[These solid tumors include but not limit to: non-small cell lung cancer, esophageal squamous cell carcinoma, melanoma, head and neck squamous cell carcinomas, hepatocellular carcinoma, gastric or gastroesophageal junction adenocarcinoma, renal cell carcinoma, etc.\]. b) dose expansion (Cervical cancer group): Histologically confirmed persistent, recurrent, or metastatic (\[International Federation of Gynecology and Obstetrics(FIGO)\] stage IVB) cervical cancer that is not eligible for curative surgery and/or definitive concurrent radiotherapy; The pathological type was squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma.; According to the investigator's judgment, it may benefit from the study drug treatment; patients with disease progression after at least one previous systemic therapy (such as systemic chemotherapy). 4. At least one measurable tumor lesion was present according to RECIST 1.1. A baseline imaging assessment could be performed up to 28 days before the first dose. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1. 6. Life expectancy ≥12 weeks 7. liver function requirements: 1. Total bilirubin (TBIL) ≤ 1.5×ULN 2. Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤ 2.5×ULN; AST or ALT ≤5×ULN if liver metastases are present; 8. Creatinine (Scr) \< 1.5×ULN and Calculated creatinine clearance (CrCL) \> 50 mL/ min (Cockroft-Gault Equation); 9. Hematology absolute neutrophil count (ANC) ≥ 1.5×109/L; hemoglobin (HGB) ≥ 90 g/L ；platelets (PLT) ≥ 75×109/L; 10. Coagulation function: International Normalized Ratio(INR)≤ 1.5×ULN; Prothrombin Time(PT)≤ 1.5×ULN; Activated Partial Thromboplastin Time(APTT)≤ 1.5×ULN. No active or clinically significant bleeding within 14 days before the first dose. 11. 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 12. Women of childbearing potential must confirm a negative serum or urine pregnancy test within 3 days prior to the initiation of study treatment; Fertile patients and their partners must agree to use effective contraceptives for the duration of study drug use and for 90 days after the last administration of study treatment.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | Up to 12 Months | Number of participants with a Dose Limiting Toxicity(DLT)\[Time Frame:During the first days\]DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria,and assessed as having a suspected or definite relationship to study drug. |
| Maximun Tolerated Dose(MTD) | Up to 24 Months | MTD or Optimal Biological Dose(OBD) and/or RP2D. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax | Up to 24 Months | Half-life time of maximum concentration |
| ORR | Up to 24 Months | Overall response rate(ORR) as measured by RECIST v1.1. |
| AUC | Up to 24 Months | AUC Area Under concentration-time Curve (AUC) |
| Cmax | Up to 24 Months | Maximum serum concentration(Cmax) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of the lymphocyte subpopulations. | Up to 24 Months | The percentage of lymphocyte subpopulations of the peripheral blood will be assessed by flow cytometry. |
| Programmed death ligand 1(PDL1) expression level | Up to 24 Months | The expression of PD-L1 in tumor tissues was detected by immunohistochemical method. |
| Tubuloglomerular Feedback(TGF-β) | Up to 24 Months | Levels of TGF-β1, TGF-β2, TGF-β3 in plasma |
Countries
China
Contacts
Primary ContactYuan Tang, Bachelor
Backup ContactKexin Hou, Master
Outcome results
None listed