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 78 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.
1. Male or female. Age ≥ 18 years.
2. 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.
3. Patients with histologically or cytologically confirmed advanced malignant solid tumor
who have received or been intolerant of all standard therapies thought to confer
4. Dose escalation stage: 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.
5. Dose expansion stage: 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
7. Life expectancy ≥3 months.
8. Adequate hepatic function as evidenced by meeting all the following requirements:
1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
2. AST and ALT ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.
9. Serum creatinine (Scr) < 1.5 × ULN and calculated creatinine clearance (CrCL) > 40
mL/min (Cockroft-Gault Equation).
10. Hematological function defined as:
1. Absolute neutrophil count ≥1,500/µL without growth factor support within 2 weeks
prior to the first dose of HB0025.
2. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks prior to
the first dose of HB0025.
3. Platelet count ≥ 75,000/µL without transfusion or recombinant human
thrombopoietin within 2 weeks prior to the first dose of HB0025.
11. Coagulation: International Normalized Ratio (INR)≤1.6 (unless receiving
anticoagulation therapy). Subjects on full-dose oral anticoagulation must be on a
stable dose (minimum duration 14 days). If receiving warfarin, the subject must have
an INR≤3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose
of study drug). Subjects on low molecular weight heparin will be allowed. Subjects
must have no active bleeding or clinically significant bleeding within 14 days prior
to first dose of study drug.
12. Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except
alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled
with hormone replacement therapy.
13. All patients will be required to provide (if available) archived paraffin blocks or at
least 10 unstained slides prior to study entry. Patients who do not have available
archival tissue will be asked (optional) to provide fresh tissue from core-needle or
Patients who meet any of the following criteria cannot be enrolled:
1. 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.
2. 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.
3. 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).
4. 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
5. 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
6. Uncontrolled diabetes mellitus with hemoglobin A1c > 8%.
7. Subjects who have received previous simultaneous therapy with a PD-1 pathway inhibitor
and a VEGF inhibitor.
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 (RT).
9. Prior stem cell, bone marrow or solid organ transplant.
10. 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
11. Any of the following infections. a) Active infection requiring intravenous therapy < 2
weeks prior to screening. b) Active tuberculosis (via medical history).
c) Patients infected with the HIV virus will be eligible if their CD4 count is > 350
cells/mm3 and the patient is on anti-retroviral therapy with an HIV viral load that is
below the level of detection. d) 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.
12. Major surgery < 4 weeks or minor surgery < 2 weeks prior to screening; wound must be
13. 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.
14. Live virus vaccines < 30 days prior to screening.
15. Pregnant or breast-feeding females.prevent (e.g., allergy to contrast agents) or treat
non-autoimmune condition (e.g. delayed hypersensitivity caused by exposure to
16. Any investigational agents or study drugs from a previous clinical study within 30
days of the first dose of study treatment.
17. 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
18. Women of childbearing potential who do not consent to use acceptable methods of birth
control during treatment and for an additional 90 days after the last administration
19. Men with a partner of childbearing potential who do not consent to use acceptable
methods of birth control during treatment and for an additional 90 days after the last
administration of HB0025.
20. Positive COVID-19 qRT-PCR and/or serology test result during screening;
21. Subjects with a history of arterial or deep venous thrombosis within 3 months before
enrollment, or patients with evidence or history of bleeding tendency within 2 months
before enrollment, regardless of severity.
22. Severe dyspnea or pulmonary dysfunction or need for continuous supportive oxygen
23. Skin wound, surgical site, wound site, mucosal ulcer or fracture not completely
24. Conditions that may cause gastrointestinal bleeding or perforation (such as duodenal
ulcer, intestinal obstruction, Crohn's disease, ulcerative colitis, large-scale
gastrectomy, etc.); patients with previous history of intestinal perforation and
intestinal fistula but not cured after surgical treatment; esophageal and gastric
25. Subjects received immune modulators treatment, including but not limited to
cyclosporine and tacrolimus, within 2 weeks before enrollment.
26. Inability to comply with study and follow-up procedures.
27. Patients who have history of interstitial lung disease or non-infectious pneumonitis
except if due to radiation therapy; such patients should be discussed with the Medical
Monitor before enrollment.
28. Subjects who in the judgement of the Investigator are not suited to participate in
29. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg and diastolic
blood pressure >80 mmHg.
30. Patients with > 2+ protein on urine dipstick should have a 24-hour urine collection;
Patients with ≥ 2 g of protein in the urine on 24-hour collection are ineligible for