A Study of HB0030 Injection in Patients With Advanced Solid Tumors

NCT05706207 | Unknown Phase 1 DMC

• 1 other identifier: HB0030-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ia single-center, open-label, dose escalation study.The objectives of this study are to evaluate the safety, toxicity, tolerability, pharmacokinetics/pharmacodynamics(PK/PD), immunogenicity, biomarkers, and antitumor activity of HB0030 in advanced solid tumor subjects.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity(DLT)

  * DLT refers to the following toxicity related to HB0030 occurred during the DLT evaluation period (the first treatment cycle): 1. Hematological Dose Limiting toxicity include： 1. Grade 4 anaemia 2. Grade IV neutropenia confirmed by reexamination. 3. Grade 3 or higher febrile neutropenia 4. Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding 2. Nonhematologic Dose Limiting toxicity include： 1. Grade IV Nonhematologic Toxicity 2. Grade 3 non-hematological toxicity, which cannot be recovered to ≤ Grade 2 within 3 days after the best treatment 3. Failure to control grade III hypertension (uncontrolled \<160/100 mmHg in 7 days with appropriate antihypertensive therapy) 4. Other toxicities judged by investigators to require permanent discontinuation of HB0030 * the above toxic reaction is evaluated by laboratory ,physical ,ECG, radiographic examination and etc. * Adverse events will be graded by NCI CTCAE v5.0

  Up to 21 days

• Maximum Tolerated Dose(MTD)

  \- Maximum Tolerated Dose is defined as the highest dose in which the number of cases of DLT is less than 1/3 of the total patients in the first treatment cycle (DLT evaluation period) of the dose increasing stage.Six subjects are required to confirm MTD

  Up to 24 Months

Secondary Outcomes (8)

• Maximum serum concentration(Cmax)

  within 48 hours after single HB0030 administered

• half-life (t1/2)

  within 3 months after first dose of HB0030 administered

• time of maximum concentration(Tmax)

  within 48 hours after single HB0030 administered

• AUClast

  Up to 24 Months

• Objective response rate (ORR)

  Up to 24 Months

Study Arms (8)

Arm 1

EXPERIMENTAL

Treatment with 0.03 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 2

EXPERIMENTAL

Treatment with 0.3 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 3

EXPERIMENTAL

Treatment with 1 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 4

EXPERIMENTAL

Treatment with 3 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 5

EXPERIMENTAL

Treatment with 10 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 6

EXPERIMENTAL

Treatment with 20 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 7

EXPERIMENTAL

Treatment with 30 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Arm 8

EXPERIMENTAL

Treatment with 40 mg/kg HB0030 injection administered intravenously

Drug: HB0030 injection

Interventions

HB0030 injection DRUG

0.03 mg/kg intravenously, every 3 weeks, till tumor progress or intolerance

Also known as: Recombinant Humanized Anti-TIGIT Monoclonal Antibody

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Age ≥ 18 years.
• Patients with histologically or cytologically confirmed advanced malignant solid tumor who have been intolerant of all standard therapies or recurrence after all standard therapies, and there is no better treatment option.
• At least one measurable tumor lesion According to RECIST criteria v1.1
• Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1
• Life expectancy ≥3 months
• Adequate organ function defined as:（No blood transfusion or hematopoietic stimulator treatment within 14 days before screening）
• Adequate Hematological function defined as:
• Absolute neutrophil count ≥1.5×109/L
• Platelet count≥75×109/L
• Hemoglobin ≥ ≥90g/L
• Adequate hepatic function defined as:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; AST or ALT ≤ 5 × ULN if subjects have liver metastases or liver cancer
• Adequate renal function defined as:
• creatinine clearance (CrCL) \> 50 mL/min (calculated by Cockcroft-Gault Equation).

You may not qualify if:

• Symptomatic central nervous system(CNS) metastases; or there is other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, which is not suitable for enrollment according to the judgment of the investigator; or patients with asymptomatic CNS metastases who are radiologically and neurologically stable \> 4 weeks following CNS directed therapy, and are on a stable or decreasing dose of corticosteroids equivalent to \< 10 mg prednisone/day for at least 2 weeks prior to study treatment are eligible for study entry.
• Active autoimmune disease or history of autoimmune disease requiring systemic therapy \< 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease, Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that has not been active in the 2 years prior to study screening are eligible.
• History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies, (except for grade 3 endocrinopathy that is managed with hormone replacement therapy).
• Use of systemic corticosteroids in a dose equivalent to \> 10 mg/day of prednisone or other immunosuppressive agent \< 2 weeks prior to screening; the use of topical, intraocular, intra-articular, intranasal or inhaled corticosteroids (systemic absorption is low) will be allowed to prevent (e.g. allergy to contrast agents) or treat non-autoimmune condition (e.g. delayed hypersensitivity caused by exposure to allergens)
• Patients who Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months before enrollment
• Serious cardiac rhythm or conduction abnormality, such as ventricular arrhythmia requiring clinical intervention, II-III degree atrioventricular block, QTcF≥450 ms, etc
• New York Heart Association（NYHA）cardiac function grade ≥ Grade II or left ventricular ejection fraction(LVEF)\<50%
• Uncontrolled arterial hypertension even after standard treatment (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg)
• Uncontrolled diabetes mellitus with hemoglobin A1c \> 8%.
• Patients who Have received TIGIT inhibitor treatment in the past
• Patients who Have received chemotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor drugs within 4 weeks before enrollment， Except for the following：
• Nitrosourea or mitomycin C within 6 weeks before the first use of the study drug
• Oral fluorouracil and small molecule targeted drugs are taken 2 weeks before the first use of the study drug or within 5 half-life of the drug(according to whichever is longer)
• The Chinese medicine with anti-tumor indication is within 2 weeks before the first use of the study drug

Sponsors & Collaborators

• Huabo Biopharm Co., Ltd.: lead
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (1)

the First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233004, China

RECRUITING

Study Officials

• huan zhou, master

  The First Affiliated Hospital of Bengbu Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

huan zhou, Master

CONTACT

+8613665527160; zhouhuanbest@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects were enrolled from low to high doses. The dose groups were 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg and 40 mg/kg, a total of 8 dose levels.For the first dose group (0.03mg/kg), the dose was increased according to the principle of accelerated titration combined with 3+3 dose acceleration.from 0.3mg/kg dose group,the study will adopt the 3+3 dose acceleration principle.

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 31, 2023
• Study Start: December 21, 2021
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: January 31, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)