A Phase Ib, Multicenter, Open-label, Dose-escalation and Dose-expansion Study of the Safety, Tolerability and Pharmacokinetics of HB002.1T in Combination With Chemotherapy in Patients With Advanced Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- HB002.1T
- Conditions
- Solid Tumor
- Sponsor
- Huabo Biopharm Co., Ltd.
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- the Maximum Tolerated Dose (MTD) of HB002.1T
- Last Updated
- 4 years ago
Overview
Brief Summary
The objectives of this study are to evaluate the safety, tolerability, and pharmacokinetic profile of HB002.1T in combination with different chemotherapy regimens administered to patients with advanced solid tumors.
Detailed Description
This study is a Phase1b, multicenter, open-label, dose-escalation and dose-expansion in selected solid tumor indications. There are two parts to this study: a dose-escalation part and a dose-expansion part. About 63-72 subjects is planned to recruit, 27\~36 subjects (9\~12 subjects each arm) will be recruited during dose-escalation period The sample size may vary depending on the DLT observed at each dose level. The conventional 3+3 design will be applied for dose escalation. This trial will evaluate two adaptive dose levels, 3 to 6 subjects will be enrolled at each dose level depending on the occurrence of dose limiting toxicities (DLTs). Cohorts of 3 subjects with metastatic or locally advanced solid tumors will receive HB002.1T at escalating dose levels in combination with different chemotherapy regimens. After determination of the Maximum tolerated dose (MTD), another 12 patients in each of 3 cohorts will be added to determine the safety, tolerability, pharmacokinetic (PK), and clinical activity of HB002.1T.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 years≤Age≤75 years
- •Histologically or cytologically confirmed advanced malignant solid tumor , including gastric cancer, ovarian cancer, cervical cancer, head and neck cancer, lung cancer, biliary tract tumor, pancreatic cancer, bladder cancer and nasopharyngeal carcinoma (not limited to the above tumor types) . And be suitable for the treatment of HB0021.T combined with 3 different chemotherapy regimen assessed by the investigators.
- •No prior radiotherapy, chemotherapy, targeted therapy, endocrine therapy or immunotherapy within 4 weeks before the first administration of HB002.1T. And no traditional herb medicines for anti-tumor within 2 weeks .
- •No prior antiangiogenic therapy such as bevacizumab, ramucirumab, apatinib or regofinib, et al.
- •At least one measurable tumor lesion as per RECIST criteria v1.1
- •ECOG performance status of 0 or 1
- •Life expectancy of at least 12 weeks
- •Meet following organ functions:
- •Absolute neutrophil count ≥2.0 x 10\^9/L(no Recombinant human granulocyte colony stimulating factor support therapy with 14 days)
- •Hemoglobin ≥100g/L(no blood transfusion or erythropoietin support treatment was received within 14 days)
Exclusion Criteria
- •Patients who meet any of the following criteria will be excluded from study entry:
- •Confirmed active CNS metastasis and /or cancerous meningitis; For patients with stable clinical symptoms for brain metastasis for more than 3months can be enrolled.
- •Positive test for hepatitis B, hepatitis C, or HIV at screening.
- •History of organ transplantationHistory of severe allergy or known severe allergic reactions (greater than grade 3 in CTCAE V5.0) to macromolecular protein preparations / monoclonal antibodies and any components of the test drug;
- •Have received other clinical trial drugs within 4 weeks before the first treatment of HB002.1T;
- •Have undergone major surgery within 4 weeks prior to screening;
- •Have undergone minor surgical procedures (including catheterization, except for PICC) within 2 days prior to screening;
- •Systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg after antihypertensive treatment (one antihypertensive drug is allowed in the baseline period, and the compound preparation is recognized as two);
- •An active infection requiring antibiotics treatment during the screening period, or an unexplained fever \> 38.5 °C occurs before the first dose;
- •Hemoptysis within 4 weeks before screening (defined as coughing with ≥1 teaspoon of blood), but do not rule out cough only with sputum or small blood clot;
Arms & Interventions
HB002.1T + Oxaliplatin+ Capecitabine
21-24 patients with advanced gastric cancer administeredHB002.1T+ Oxaliplatin+ Capecitabine combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: HB002.1T
HB002.1T + Oxaliplatin+ Capecitabine
21-24 patients with advanced gastric cancer administeredHB002.1T+ Oxaliplatin+ Capecitabine combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Oxaliplatin
HB002.1T + Oxaliplatin+ Capecitabine
21-24 patients with advanced gastric cancer administeredHB002.1T+ Oxaliplatin+ Capecitabine combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Capecitabine
HB002.1T + Paclitaxel + Carboplatin
21-24 patients with advanced ovarian cancer, cervical cancer, head and neck cancer or lung cancer (not limited to the above tumor types) administered HB002.1T + Paclitaxel + Carboplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: HB002.1T
HB002.1T + Paclitaxel + Carboplatin
21-24 patients with advanced ovarian cancer, cervical cancer, head and neck cancer or lung cancer (not limited to the above tumor types) administered HB002.1T + Paclitaxel + Carboplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Paclitaxel
HB002.1T + Paclitaxel + Carboplatin
21-24 patients with advanced ovarian cancer, cervical cancer, head and neck cancer or lung cancer (not limited to the above tumor types) administered HB002.1T + Paclitaxel + Carboplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Carboplatin
HB002.1T + Gemcitabine + Cisplatin
21-24 patients with advanced biliary tract tumor, pancreatic cancer, bladder cancer or nasopharyngeal carcinoma (not limited to the above tumor types) administered HB002.1T + Gemcitabine + Cisplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: HB002.1T
HB002.1T + Gemcitabine + Cisplatin
21-24 patients with advanced biliary tract tumor, pancreatic cancer, bladder cancer or nasopharyngeal carcinoma (not limited to the above tumor types) administered HB002.1T + Gemcitabine + Cisplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Gemcitabine
HB002.1T + Gemcitabine + Cisplatin
21-24 patients with advanced biliary tract tumor, pancreatic cancer, bladder cancer or nasopharyngeal carcinoma (not limited to the above tumor types) administered HB002.1T + Gemcitabine + Cisplatin combination every 3 weeks in a 21-day cycle, total 18cycles
Intervention: Cisplatin
Outcomes
Primary Outcomes
the Maximum Tolerated Dose (MTD) of HB002.1T
Time Frame: up to 3 weeks
Will be determined by dose limiting toxicity. MTD defined as the highest dose level with no more than 1 patient with DLT out of 6 patients that are treated.
Secondary Outcomes
- Immunogenicity of HB002.1T(through study completion, up to 24 weeks)
- overall response rate (ORR)(through study completion, up to 24 weeks)
- disease control rate (DCR)(through study completion, up to 24 weeks)
- Progression free survival (PFS)(through study completion, up to 24 weeks)
- duration of response (DOR)(through study completion, up to 24 weeks)