晚期實體腫瘤或復發及難治型典型何杰金氏淋巴瘤

本試驗目的為針對18歲及以上晚期實體腫瘤或復發及難治型典型何杰金氏淋巴瘤受試者，探討 HCB301 IV 輸注的安全性、耐受性、藥物動力學及初步療效。

注射液劑

HCB301

27D

90mg/6mL

-發生 AE、SAE、TEAE、DLT 的數量/發生率及受試者百分比
-從血清檢體中推導的 ADA/nADA 濃度
-HCB301單一療法的 MTD 和 RDE

Informed Consent
1. Subjects are able to understand and willing to provide signed informed consent as described in
Appendix 1, Section 10.1.3, which includes compliance with the requirements and restrictions
listed in the informed consent form (ICF) and in this protocol, including study visits and studyrelated
procedures.
Age and Sex
2. Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed
consent.
Type of Subject and Disease Characteristics
3. With histologically/cytologically confirmed diagnosis of the following indications as described
below:
o For subjects with advanced solid tumors: subjects with histologically or cytologically
confirmed advanced solid tumors who have relapsed and refractory and should have no
options for standard or approved therapies known to potentially confer clinical benefit;
o For subjects with relapsed and refractory classical Hodgkin lymphomas: subjects with
histologically or cytologically confirmed classical Hodgkin lymphomas that have relapsed
and refractory to at least 2 prior lines of systemic therapy.
4. Must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 (for subjects with advanced solid tumors) OR must have classical
Hodgkin lymphoma that is measurable or assessable for response.
5. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at
Screening.
6. Able to provide tumor tissue samples.
7. Have a life expectancy of ≥12 weeks (according to the Investigator’s judgment).
8. Have adequate organ function, as indicated by the following laboratory parameters listed in the
table below (had not received a blood transfusion, apheresis infusion, erythropoietin,
granulocyte colony-stimulating factor, and other relevant medical support within 14 days
before the administration of the first dose of the study drug).
Contraceptive/Barrier Requirements
9. a) Female subjects should meet at least one of the following criteria before they can participate
in the study:
i. Females who have no childbearing potential (i.e., physiologically incapable of
pregnancy), including those who have undergone hysterectomy, bilateral
oophorectomy, or bilateral salpingectomy;
ii. Postmenopausal (total cessation of menses for ≥1 year);
iii. Women of childbearing potential (WOCBP) must have a negative serum pregnancy
test during the Screening Period (within 7 days before the first dose of the study drug),
must not be lactating, and must be willing to practice a highly effective contraceptive
method throughout the study (i.e., from study entry up to 6 months after the last dose
of the study drug). A highly effective method of contraception is defined as one that
results in a low failure rate (i.e., < 1% per year when used consistently and correctly).
See Appendix 4 for the definition of WOCBP and highly effective methods of
contraception.
b) Male subjects are eligible to participate in the study if they have undergone a vasectomy or
agree to use a highly effective method of contraception and refrain from donating sperm from
study entry up to 6 months after the last dose of the study drug.

Medical Conditions
1. With a known history of hypersensitivity to any components of the study drug.
2. Primary tumor in the central nervous system (CNS), or active or untreated CNS metastases
and/or carcinomatous meningitis. Subjects with previously treated brain metastases may
participate, provided they are clinically stable for at least 28 days and have no evidence of new
or enlarging brain metastases and no requirements for high-dose corticosteroids 14 days before
dosing with the study drug. Subjects on low-dose corticosteroids (<20 mg prednisone or
equivalent per day) may participate.
3. Subjects who have undergone major surgery or have undergone radical radiotherapy within 28
days before the first dose of the study drug or have undergone palliative radiotherapy within
14 days before the first dose of the study drug, or have used a radioactive drug (Strontium,
Samarium, etc.) within 56 days before the first dose of the study drug.
4. Clinically significant cardiovascular condition, including:
• History of congestive heart failure (New York Heart Association Class >2);
• History of unstable angina within 6 months before the first dose of the study drug;
• New-onset angina or myocardial infarction within 6 months before the first dose of the
study drug;
• New-onset of atrial fibrillation, supraventricular arrhythmia, or ventricular arrhythmia
within 6 months before the first dose of the study drug and still in unstable condition and
requiring treatment or intervention. History of atrial fibrillation, supraventricular
arrhythmia, or ventricular arrhythmia will be allowed, provided the condition is stably
controlled.
5. Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated
by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI-CTCAE)
version 5.0 or baseline, except alopecia and anemia (Note: subjects with chronic Grade 2
toxicities which are well managed and stable may be eligible per the discretion of the
Investigator after discussion with the Sponsor and medical monitor, e.g., Grade 2
chemotherapy-induced neuropathy.)
6. With known inherited or acquired bleeding disorders or bleeding diathesis.
7. Have RBC transfusion dependence defined as requiring more than 2 units of RBC transfusions
during the 4 weeks before Screening.
8. With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last
3 months before Screening.
9. Presence of known active or suspected autoimmune diseases requiring systemic
immunosuppressive medications. Subjects achieving stable status and requiring no treatment
with systemic immunosuppressive therapies 3 months before Screening are allowed to be
enrolled.
Prior/Concomitant Therapy/Treatment
10. Any investigational or approved systemic cancer therapy (including chemotherapy,
immunotherapy, hormonal therapy, and herbal/alternative therapies with anti-cancer
indications or targeted therapy) administered within 21 days or 5 half-lives, whichever is
shorter, before the first dose of the study drug.
11. Any investigational device was used within 28 days before the first dose of the study drug.
12. Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight
heparin and factor Xa inhibitors is permitted on a case-by-case basis. There will be no
restriction for daily aspirin ≤ 100 mg/QD.
13. Have used herbal medication within 14 days before the first dose of the study drug.
14. Have received any treatment targeting the SIRPα-CD47 or TGF-β pathway.
15. Received or planning to receive live virus or bacterial vaccine within 28 days before the first
dose of the study drug and while the subject is receiving the study drug. Subjects who require
Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) vaccination while
on the study drug must receive a non-live vaccine (e.g., one based on messenger RNA [mRNA]
or fully inactivated/genetically modified viruses incapable of replication).
16. Subjects who have other malignancies requiring treatment within 2 years before the first dose
of the study drug will be excluded, except for radically treated locally curable basal or
squamous cell skin cancer and other malignancies that have been treated with no relapse within
2 years.
Diagnostic Assessments
17. History or presence of an abnormal ECG that, in the Investigator’s opinion, is clinically
meaningful (including QT interval corrected for heart rate using Fridericia’s correction
[QTcF] >470 msec at Screening, pacemaker installation, or previous diagnosis of congenital
long QT syndrome).
Infections
18. An uncontrolled acute infection, an active infection requiring systemic treatment, or subjects
who have received systemic antibiotics within 14 days before the first dose of the study drug
(Note: prophylaxis use of systemic antibiotics treatment for upper tract infection is allowed as
long as there is no violation of the requirement of concomitant medications).
19. Known history of human immunodeficiency virus (HIV) infection and/or acquired
immunodeficiency syndrome or positive HIV testing having CD4+ T-cell counts <350 cells/μL
or subjects with unknown HIV infection status who are unwilling to undergo HIV testing.
20. Known active hepatitis B or C. Subjects with hepatitis B virus surface antigen (HBsAg) or
hepatitis C virus (HCV) antibody positive test results during Screening must be further tested
for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) titer (excluding subjects with a DNA
titer of more than 2500 copies [cps]/mL or 500 IU/mL) and HCV ribonucleic acid (RNA)
(excluding subjects with an HCV RNA concentration exceeding the lower detection limit of
the assay) to exclude active hepatitis B or hepatitis C infection requiring treatment. Hepatitis
B virus carriers, i.e., subjects with stable hepatitis B infection after drug treatment (DNA titer
not exceeding 2500 cps/mL or 500 IU/mL) and hepatitis C infected subjects who received
treatment and achieved sustained virologic response for at least 12 weeks can be enrolled.
(Note: If the lower detection limit of the HBV DNA assay is higher than 2500 cps/mL or
500 IU/mL, the subjects with an HBV DNA assay result lower than the lower detection limit
of the assay can be enrolled.)
21. Active tuberculosis.
Other Exclusion Criteria
22. Known to have a history of alcoholism or drug abuse.
23. Any other medical (e.g., Child-Pugh class B or C, pulmonary, metabolic, congenital,
endocrinal or CNS disease, etc.), psychiatric, or social condition deemed by the Investigator to
be likely to interfere with a subject’s rights, safety, welfare or ability to sign informed consent,
cooperate and participate in the study, or interfere with the interpretation of the results.
24. Recipients of an organ allograft or allogeneic stem cell transplantation.