A Study of Injection HB0025 in Patients With Advanced Solid Tumors

NCT04678908 | Unknown Phase 1 FDA Drug

• 1 other identifier: HB0025-01
• Study Type: interventional
• Target: 154
• Locations: 2 countries
• Sites: 6

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.

Conditions

Tumor, Subjects

Outcome Measures

Primary Outcomes (3)

• Safety assessment in dose-escalation phase

  Safety profile including adverse events, changes in safety assessment parameters (e.g. incidence of AEs, vital signs, ECGs, clinical laboratory results and DLTs);

  240 Days

• Safety assessment in dose-escalation phase

  MTD or OBD and/or RP2D.

  240 Days

• Efficacy assessment in dose-expansion phase

  ORR as measured by RECIST v1.1.

  Up to 24 Moths

Secondary Outcomes (12)

• PK parameters in dose-escalation phase

  240 Days

• ORR assessment in dose-escalation phase

  Up to 24 Months

• DCR assessment in dose-escalation phase

  Up to 24 Months

• DOR assessment in dose-escalation phase

  Up to 24 Months

• PFS assessment in dose-escalation phase

  Up to 24 Months

Study Arms (1)

HB0025

EXPERIMENTAL

HB0025 IV every 2 weeks (q2w)

Drug: HB0025

Interventions

HB0025 DRUG

Patients will be assigned to dose regimens in the order of enrollment, and they will receive their assigned fixed dose of HB0025 via intravenous infusion.

Also known as: Recombinant Humanized Anti-PD-L1 Monoclonal Antibody-VEGFR1 Fusion Protein

HB0025

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.
• 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).
• ii) Assessed by the investigator as likely to benefit from the study drug therapy Patient with disease progression from at least one previous systemic treatment or who are intolerant to the current standard treatment as determined by the investigator.
• c) Other advanced solid tumor cohort: Patient with other advanced solid tumors that are not suitable for radical therapy or relapse /metastasis diagnosed histopathological and/or cytologically according to the type of tumor that responds well during the dose escalation phase.
• \. Accelerated escalation: Evaluable disease per RECIST v1.1 for solid tumors; Radiographic disease assessment at baseline can be performed up to 28 days prior to the first dose.
• \. 3+3 dose escalation and dose expansion cohort: At least one measurable tumor lesion as per RECIST criteria v1.1 defined as having at least one dimension with a minimum size of 10 mm in the longest diameter by CT or MRI scan for non-nodal lesions or ≥15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 28 days prior to the first dose.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

You may not qualify if:

• 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.
• Concurrent malignancy \< 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma. Patients with prostate cancer that is under active surveillance are eligible.
• Any of the following infections. 1) Active infection requiring intravenous therapy \< 2 weeks prior to screening. 2) Active tuberculosis (via medical history). 3) Positive test for HIV antibody at screening. 4) Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer \< 1000 cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled.
• Major surgery \< 4 weeks or minor surgery \< 2 weeks prior to screening; wound must be fully healed.
• History of severe allergic reactions, Grade 3-4 allergic reaction to treatment with another monoclonal antibody, or known to be allergic to protein drugs or recombinant proteins or excipients in HB0025 drug formulation.
• Live virus vaccines \< 30 days prior to screening.

Sponsors & Collaborators

• Huabo Biopharm Co., Ltd.: lead

Study Sites (6)

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233000, China

RECRUITING

Central Hospital Affiliated to ShanDong First Medical University

Jinan, Shandong, 250000, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250000, China

RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, 726000, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 201210, China

RECRUITING

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Anthony Tolcher

CONTACT

210-580-9500; atolcher@nextoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 22, 2020
• Study Start: March 10, 2021
• Primary Completion: February 2, 2024
• Study Completion: May 23, 2024
• Last Updated: June 1, 2022

Record last verified: 2022-05

Locations

US (1); CN (5)