A Phase 1, Multicenter, Open-label, Dose-escalation and Dose-expansion Study of the Safety and Pharmacokinetics of HB0025 in Patients With Advanced Solid Tumors

Huabo Biopharm Co., Ltd.6 sites in 2 countries154 target enrollmentMarch 10, 2021

ConditionsTumor, Subjects

InterventionsHB0025

DrugsHB0025

Overview

Phase: Phase 1
Intervention: HB0025
Conditions: Tumor, Subjects
Sponsor: Huabo Biopharm Co., Ltd.
Enrollment: 154
Locations: 6
Primary Endpoint: Safety assessment in dose-escalation phase
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, open-label, dose escalation and expansion study. During the study, subjects will be evaluated for safety, toxicity, tolerability, PK/PD, immunogenicity, biomarkers, and antitumor activity of HB0025. The phase I study will enroll up to 154 subjects with advanced solid tumors who have progressed on or after standard of care therapy and for whom there is no further treatment available that in the judgement of the patient's physician would be beneficial. One cycle is defined as 28 days.

Detailed Description

Dose escalation phase Approximately 19 to 74 subjects will receive escalating doses on HB0025 monotherapy. The escalating dose phase is composed of an accelerated titration design and a conventional 3+3 design. During the dose escalation, when a given dose level completes the DLT observation period, an evaluation of PK, PD, biomarkers, tolerability and efficacy will be performed and if this dose level is considered as a possible candidate dose level for OBD. Determination of MTD or OBD will be expanded to a total of 6 subjects (if not already done due to observation of a DLT). After the MTD or OBD is determined, the dose group will continue to recruit subjects until the total number of subjects reaches 10 to confirm that the MTD or OBD is RP2D. Dose escalation phase Approximately 80 subjects will be enrolled into expansion doses on HB0025. During the dose escalation process, dose expansion studies will be conducted based on the preliminary determination of RP2D and the expanded tumor types.

Registry

clinicaltrials.gov

Start Date

March 10, 2021

End Date

May 23, 2024

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Huabo Biopharm Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female. Age ≥ 18 years.
•Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
•Dose escalation phase: Patients with histologically or cytologically confirmed advanced malignant solid tumor who have received or been intolerant of all standard therapies thought to confer clinical benefit. These solid tumors include but are not limited to hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), renal carcinoma (RCC), endometrial carcinoma, etc.
•Dose expansion phase:
•a) Advanced HCC Cohort:
•i) Unresectable HCC with diagnosis confirmed by histology/cytology or clinical criteria.
•ii) Assessed by the investigator as likely to benefit from the study drug therapy; and should have progressed at least one prior systemic therapy regimen which could include but not limited to sorafenib, lenvatinib, donafenib, systematic chemotherapy,etc.
•iii)Child-Pugh Classification with score ≤ 6 points.(See Appendix13.6 for criteria) VI)HBsAg test is negative.Patients with active hepatitis B virus (HBV) infection must have a viral load \< 500 IU/mL within 28 days prior to start of study treatment and be on suppressive therapy (per local standard of care) for a minimum of 14 days prior to start of study treatment and for the length of the study.
•b) Advanced Renal Cell Carcinoma Cohort and Advanced Endometrial Carcinoma Cohort:
•i) Histopathological and/or cytological diagnosis of patients with advanced clear cell renal carcinoma, advanced endometrial carcinoma, who are not suitable for radical treatment or have relapsed/metastatic disease; Advanced clear cell renal carcinoma should be assessed as medium-high risk by the International Metastatic Renal Cell Carcinoma Database Alliance (IMDC).

Exclusion Criteria

•Patients who meet any of the following criteria cannot be enrolled:
•Symptomatic central nervous system metastases; 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).
•Cerebrovascular accident (CVA), Transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heart failure \< 6 months of study entry; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) \> 470 milliseconds (ms) (males) or \> 480 ms (females) obtained from three ECGs; uncontrolled arrhythmia \< 3 months of study entry. Patients with rate-controlled arrhythmias may be eligible for study entry at discretion of the Investigator.
•Uncontrolled diabetes mellitus with hemoglobin A1c \> 8%.
•Subjects who have received previous simultaneous therapy with a PD-1 pathway inhibitor and a macromolecule VEGF inhibitor (Bevacizumab, Ramucirumab, etc).
•Anticancer therapy or radiation \< 5 half-lives or 4 weeks (whichever is shorter) prior to study entry; palliative radiotherapy to a single area \< 2 weeks prior to study screening is permitted. Measurable lesions cannot be previously irradiated unless they have demonstrated growth after radiation therapy (RT).
•Prior stem cell, bone marrow or solid organ transplant.