A Study Evaluating the Safety and Efficacy of HB0028 in Subjects With Advanced Solid Tumors

NCT06223308 | Unknown Phase 1

• 1 other identifier: HB0028-01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor; Cervical Cancer

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability

  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.

  Up to 12 Months

• Maximun Tolerated Dose(MTD)

  MTD or Optimal Biological Dose(OBD) and/or RP2D.

  Up to 24 Months

Secondary Outcomes (4)

• AUC

  Up to 24 Months

• Cmax

  Up to 24 Months

• Tmax

  Up to 24 Months

• ORR

  Up to 24 Months

Other Outcomes (3)

• Percentage of the lymphocyte subpopulations.

  Up to 24 Months

• Programmed death ligand 1(PDL1) expression level

  Up to 24 Months

• Tubuloglomerular Feedback(TGF-β)

  Up to 24 Months

Study Arms (1)

HB0028

EXPERIMENTAL

HB0028 IV every 3 weeks (q3w)

Drug: HB0028

Interventions

HB0028 DRUG

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).

Also known as: Anti-PD-L1 and TGF-β bifunctional fusion protein

HB0028

Eligibility Criteria

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

You may qualify if:

• Patients must meet all the following criteria to be eligible for participation in this study:
• Male or female. Age ≥ 18 years.
• The subject is able to understand and willing to sign the Informed Consent Form(ICF); willing and able to comply with all study procedures.
• 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).
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Life expectancy ≥12 weeks
• liver function requirements:
• Total bilirubin (TBIL) ≤ 1.5×ULN
• Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤ 2.5×ULN; AST or ALT ≤5×ULN if liver metastases are present;
• Creatinine (Scr) \< 1.5×ULN and Calculated creatinine clearance (CrCL) \> 50 mL/ min (Cockroft-Gault Equation);
• Hematology absolute neutrophil count (ANC) ≥ 1.5×109/L; hemoglobin (HGB) ≥ 90 g/L ；platelets (PLT) ≥ 75×109/L;
• 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.
• 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

You may not qualify if:

• Have clinically active central nervous system (CNS) metastases. Patients with previously-treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable (\>4 weeks) and asymptomatic. Patients with asymptomatic brain metastasis or subjects who are symptomatically stable after treatment and are on \< 10 mg/d prednisone or equivalent are eligible.
• dose expansion (Cervical cancer group): Hydronephrosis, which could not be relieved by clinical treatment
• 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, intraarticular, intranasal, or inhaled corticosteroids and systemic steroids to prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g., delayed hypersensitivity caused by exposure to allergens) or short course (\< 5 days) will be allowed
• 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; uncontrolled arrhythmia \< 3 months of study entry; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) \> 470 milliseconds (ms) obtained from three ECGs;
• uncontrolled diabetes, glycosylated hemoglobin HbA1c \>8%；
• 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 (According to RECIST v1.1).
• Patients who have previously received allogeneic stem cell, Bone marrow or solid organ transplantation.
• The following infections are present
• Active infection requiring intravenous treatment within 2 weeks before screening
• Active Pulmonary tuberculosis
• Positive results for HIV test
• Active hepatitis B or C. Patients with asymptomatic hepatitis B virus carriers (HBV DNA titer \< 1000 cps/mL or 200 IU/mL) or cured hepatitis C virus(HCV)(negative HCV RNA test) may be enrolled;
• Major surgery \< 4 weeks prior to the first dose; Minor surgery \< 2 weeks prior to the first dose

Sponsors & Collaborators

• Shanghai Huaota Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Jing Wang, MD/PHD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuan Tang, Bachelor

CONTACT

021-51320053; yuan.tang@huaota.com

Kexin Hou, Master

CONTACT

021-51320053; kexin.hou@huaota.com

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: December 24, 2023
• First Posted: January 25, 2024
• Study Start: September 9, 2022
• Primary Completion: May 1, 2024
• Study Completion: October 1, 2024
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)