Trial Title:
A Study Evaluating the Safety and Efficacy of HB0028 in Subjects With Advanced Solid Tumors
NCT ID:
NCT06223308
Condition:
Advanced Solid Tumor
Cervical Cancer
Conditions: Official terms:
Neoplasms
Uterine Cervical Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HB0028
Description:
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).
Arm group label:
HB0028
Other name:
Anti-PD-L1 and TGF-β bifunctional fusion protein
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.
Detailed description:
This is a phase I/II, multicenter, open-label, first-in-human study in patients with
advanced solid tumors. During the phase I study, the safety and tolerability of HB0028
will be evaluated in patients with advanced solid tumors. In the phase II study, the
safety and efficacy of HB0028 at the RP2D will be evaluated in cohorts of patients with
specific solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must meet all the following criteria to be eligible for participation in
this study:
1. Male or female. Age ≥ 18 years.
2. The subject is able to understand and willing to sign the Informed Consent
Form(ICF); willing and able to comply with all study procedures.
3. 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).
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
6. Life expectancy ≥12 weeks
7. liver function requirements:
1. Total bilirubin (TBIL) ≤ 1.5×ULN
2. Aspartate aminotransferase(AST) and Alanine aminotransferase(ALT) ≤
2.5×ULN; AST or ALT ≤5×ULN if liver metastases are present;
8. Creatinine (Scr) < 1.5×ULN and Calculated creatinine clearance (CrCL) > 50 mL/
min (Cockroft-Gault Equation);
9. Hematology absolute neutrophil count (ANC) ≥ 1.5×109/L; hemoglobin (HGB) ≥ 90
g/L ；platelets (PLT) ≥ 75×109/L;
10. 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.
11. 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
12. Women of childbearing potential must confirm a negative serum or urine
pregnancy test within 3 days prior to the initiation of study treatment;
Fertile patients and their partners must agree to use effective contraceptives
for the duration of study drug use and for 90 days after the last
administration of study treatment.
Exclusion Criteria:
- Exclusion Criteria Patients are excluded from the study if any of the following
criteria apply:
1. 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.
2. dose expansion (Cervical cancer group): Hydronephrosis, which could not be
relieved by clinical treatment
3. 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.
4. 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).
5. 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
6. 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;
7. uncontrolled diabetes, glycosylated hemoglobin HbA1c >8%；
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).
9. Patients who have previously received allogeneic stem cell, Bone marrow or
solid organ transplantation.
10. The following infections are present
1. Active infection requiring intravenous treatment within 2 weeks before
screening
2. Active Pulmonary tuberculosis
3. Positive results for HIV test
4. 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;
11. Major surgery < 4 weeks prior to the first dose; Minor surgery < 2 weeks prior
to the first dose
12. History of severe allergic reactions, grade 3-4 allergic reactions to treatment
with another monoclonal antibody, or known to be allergic to protein drugs or
recombinant proteins or excipients in HB0028 drug formulation;
13. Have received or will receive a live vaccine within 30 days prior to the
screening.
14. Patients who have participated in any clinical trial of a drug or medical
device within 30 days prior to the first dose
15. Any other serious underlying medical condition (e.g., active gastric ulcer,
uncontrolled seizures, cerebrovascular incidents, gastrointestinal bleeding,
severe signs and symptoms of coagulation and clotting disorders, cardiac
conditions), or psychiatric, psychological, familial condition or geographical
location that, in the judgment of the Investigator, may interfere with the
planned staging, treatment and follow-up, affect patient compliance or place
the patient at high risk from treatment.
16. Positive COVID-19 quantitative real time (qRT) polymerase chain reaction (PCR)
or rapid screening test during screening;
17. Patients with a history of arterial or deep vein thrombosis within 6 months
before enrollment; evidence or history of a bleeding tendency within 2 months
before enrollment
18. Severe dyspnea, pulmonary insufficiency or the need for continuous supportive
oxygen therapy
19. The surgical site, the wound site, the mucous membrane severely ulcerated, or
the fracture did not heal completely
20. Conditions that may cause bleeding or perforation of the digestive tract (such
as duodenal ulcer, intestinal obstruction, Crohn's disease, Ulcerative colitis,
large gastrectomy and small bowel resection, etc.); Patients with a history of
intestinal perforation and fistula, who were not cured after surgical
treatment; Esophageal and gastric varices
21. Immunomodulatory therapy was administered within 2 weeks before enrollment
(including but not limited to cyclosporine and tacrolimus)
22. Have history of interstitial lung disease or non-infectious pneumonitis, except
from radiotherapy (the enrollment of subjects needs to be considered after
discussion with MM);
23. Other conditions which would make it inappropriate for the patient to
participate as judged by the investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410013
Country:
China
Status:
Recruiting
Contact:
Last name:
Jing Wang, MD/PHD
Phone:
0731-88651900
Email:
wangjing0081@126.com
Contact backup:
Last name:
Yan Tang, MD/PHD
Phone:
0731-88651900
Email:
tangyan6049@hnca.org.cn
Investigator:
Last name:
Jing Wang, MD/PHD
Email:
Principal Investigator
Start date:
September 9, 2022
Completion date:
October 1, 2024
Lead sponsor:
Agency:
Shanghai Huaota Biopharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Shanghai Huaota Biopharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06223308
