Trial Title:
Study on the Tolerability and Pharmacokinetics of HX009 in Patients With Advanced Solid Tumors
NCT ID:
NCT05731752
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Antibodies, Bispecific
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HX009
Description:
The subjects will receive HX009 treatment via IV infusion once every 2 weeks at different
dose escalation cohorts
Arm group label:
HX009
Other name:
Recombinant humanized anti-CD47/PD-1 bifunctional antibody
Summary:
This is an open, multiple-dose administration dose exploratory clinical phase I study to
evaluate the safety, tolerability, and PK profile of HX009 Injection in patients with
advanced solid tumors and to provide a preliminary measure of its antitumor efficacy. It
includes Phase Ia and Phase Ib.
phase Ia is a dose exploratory study to evaluate safety, tolerability, and to determine
the MTD and/or RP2D.The sponsor and investigator will adjust the magnitude of the dose
escalation and the dosing cycle based on the safety and tolerability of HX009 Injection
and the PK data that have been obtained, as well as decide whether to add an unplanned
dose or dosing cycle to the trial, and recommend the RP2D.The Ia phase dose escalation
design model is shown below. The planned dosing cycle for this study is once every 2
weeks (14 days) (Q2W) with IV HX009.
Based on the result of phase 1a,10 mg/kg Q2W was the recommended dose for phase 1b. The
aimed population for 1b is patients diagnosed with advanced melanoma, and divided into
two cohorts:: cohort A ,untreated patients with unresectable or metastatic advanced
melanoma;and Cohort B, patients with unresectable or metastatic malignant melanoma that
had been treated with immune checkpoint inhibitor therapy. The enrollment of Cohort B
will start first.,and whether the cohort A will be initiated depends on the results of
the cohort B .The up to 80 patients will be enrolled in Phase Ib.
Detailed description:
The study is divided into a screening, treatment, and follow-up period. The Treatment
Period may continue to be administered until the investigator determines that the subject
no longer benefits, or the subject develops intolerable toxicity, or the subject
withdraws informed consent, or the disease progresses or is treated with an
antineoplastic agent other than those specified in the protocol, or the subject dies, or
is lost to follow-up, or a Phase Ib subject has been administered for 2 years (whichever
occurs earliest).
Subjects who withdraw from the study/terminate treatment for any reason are required to
return for 1 follow-up visit after the last dose, to collect as many RO blood samples as
possible after discontinuation (only partial subjects in Phase Ib), and to collect
clinical data on safety as well as survival. During the subsequent follow-up period (for
Phase Ib only), subjects or family members will receive a telephone visit to inquire
about survival and antitumor therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
In Phase Ia.
Subjects must meet all of the following enrollment criteria to be enrolled in this study:
1. Voluntarily sign an informed consent form, understand the study and be willing to
follow and be capable of completing all trial procedures;
2. Male or female, age 18-70 years (including borderline values);
3. ECOG score: 0 to 1;
4. Advanced malignant solid tumors diagnosed by cytology or histopathology and after
failure of standard treatment (disease progression or intolerable) or in the absence
of effective therapies;
5. Subjects must have at least one extracranial lesion for efficacy assessment
according to the Solid Tumor Evaluation Criteria (RECIST 1.1), including both
measurable and non-measurable lesions. The number of subject cases with all
non-measurable lesions must not exceed 1/3 of the total enrollment;
6. Expected survival ≥ 12 weeks;
7. If prior antitumor therapy has been received, the following are required:
- ≥ 3 weeks between systemic radiation therapy and the first dose, and ≥ 2 weeks
between localized radiation therapy or radiation therapy for bone metastases;
- Prior chemotherapy, immunotherapy (PD-1 antibody, PD-L1 antibody, or CTLA-4
antibody, etc.), biologic therapy (tumor vaccine, cytokine, or growth factor
for cancer control), and targeted therapy ≥ 4 weeks from the first
administration interval (small molecule targeted agent therapy ≥ 2 weeks from
the first administration interval);
- Prior immunotherapy with PD-1 antibody, PD-L1 antibody, or CTLA-4 antibody
without permanent discontinuation due to prior immunotherapy;
- Prior treatment with a significant anti-tumor herbal or proprietary Chinese
medicine ≥ 2 weeks from the first dose;
8. In the case of patients with asymptomatic Central Nervous System (CNS) metastases or
treated asymptomatic brain metastases, be free of disease progression by Computed
Tomography (CT) or Magnetic Resonance Imaging (MRI), be stable for at least 4 weeks,
and not require steroid medication;
9. Have appropriate organ and hematopoietic function and no severe cardiac, pulmonary,
hepatic, or renal dysfunction or immunodeficiency based on the following laboratory
tests
in phase Ib
Subjects must meet all of the following enrollment criteria to be enrolled in this trial:
1. Voluntarily sign an informed consent form, understand the study and be willing to
follow and be capable of completing all trial procedures;
2. Male or female, age 18-75 years (including borderline values);
3. ECOG score: 0 to 1;
4. Unresectable/metastatic advanced melanoma diagnosed by cytology or histopathology;
5. Cohort A: No prior systemic therapy for advanced melanoma (prior neoadjuvant and
adjuvant therapy with last dose completed before 6 months can be enrolled). Cohort
A: No prior systemic therapy for advanced melanoma (previous neoadjuvant and
adjuvant therapy, completed before 6 months of last dose) Cohort B: Disease
progression after treatment with immune checkpoint inhibitors ;
6. Subjects must have at least one measurable lesion according to the Solid Tumor
Evaluation Criteria (RECIST 1.1);
7. Expected survival ≥ 12 weeks;
8. have adequate organ and hematopoietic function, and have laboratory results that
meet the requirements
Exclusion Criteria:
in Phase Ia:
- Subjects with any of the following are not eligible for enrollment in this study:
1. Those who have developed another malignancy within 5 years prior to enrollment,
with the exception of cured carcinoma in situ of the cervix and cured basal
cell carcinoma of the skin;
2. Failure to recover from adverse effects of prior therapy to a CTCAE 5.0 grade
score of ≤ grade 1, except for residual alopecia areata effects;
3. Subjects with active, or history of, autoimmune disease with potential for
relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory
bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis,
glomerulonephritis, etc.), or at high risk (e.g., have received an organ
transplant requiring immunosuppressive therapy). However, subjects with the
following diseases are allowed to enroll:
- Type 1 diabetes mellitus that has stabilized with the use of fixed-dose insulin;
- Autoimmune hypothyroidism requiring only hormone replacement therapy;
- Skin disorders that do not require systemic therapy (e.g., eczema, rashes covering
less than 10% of the body surface, psoriasis without ophthalmologic symptoms, etc.);
4) Anticipated major surgery during this study including the 28-day screening
period; 5) Subjects requiring treatment with systemic corticosteroids (dose
equivalent to >10 mg prednisone/day) or other immunosuppressive medications within
14 days prior to the first dose or during the study period; enrollment is permitted
in the following cases:
- Subjects are permitted to use topical topical or inhaled glucocorticoids;
- Short-term (≤ 7 days) use of glucocorticoids for prophylaxis or treatment of
non-autoimmune allergic diseases is permitted; 6) Currently suffering from sudden
lung disease, interstitial lung disease, interstitial pneumonia, pulmonary fibrosis,
acute lung disease, radiation pneumonitis; 7) systemic diseases that have not been
controlled and stabilized by treatment, such as cardiovascular diseases (unstable
angina pectoris or myocardial infarction before 6 months, etc.) diabetes mellitus,
hypertension, etc; 8) arterial or venous thrombosis or embolic events such as
cerebrovascular accidents (including transient ischemic attacks), deep vein
thrombosis or pulmonary embolism within 6 months prior to the first dose; 9) History
of infection with human immunodeficiency virus, or other acquired, congenital
immunodeficiency disease, or history of organ transplantation, or stem cell
transplantation; 10) a history of tuberculosis, or a history of tuberculosis disease
at the time of screening 11) those with active chronic hepatitis B or active
hepatitis C Hepatitis B virus carriers, hepatitis B stabilized by drug therapy (DNA
titer must not be higher than 500 IU/mL or copy number <1000copies/ml) and patients
with cured hepatitis C (negative HCV RNA test) may be enrolled; 12) Those who have
had a serious infection within 4 weeks prior to the first dose or who have had an
active infection requiring oral or intravenous antibiotic therapy within the
previous 2 weeks;
In phase Ib :
Phase Ib Exclusion Criteria
Subjects with any of the following are not eligible for enrollment in this study:
1. Histologic or pathologic diagnosis of choroidal malignant melanoma;
2. Patients with brain metastases, except those who have been treated and are
symptomatically stable. Require ongoing corticosteroids as treatment for CNS
disorders, allowing stable doses of anticonvulsant therapy.
3. Malignancies other than malignant melanoma that have occurred within 5 years prior
to enrollment, with the exception of malignancies with negligible risk of metastasis
or death and/or curative treatment (e.g., adequately treated carcinoma in situ of
the cervix, basal or squamous cell skin carcinoma, limited prostate cancer, ductal
carcinoma in situ, or stage I uterine cancer);
4. Uncontrolled pleural effusion, abdominal effusion, or pericardial effusion requiring
repeated drainage. Those with indwelling drainage tubes are allowed to be enrolled;
5. History of blood transfusion within the last 3 months;
6. hemolytic anemia, autoimmune thrombocytopenia, or Evan syndrome within the last 3
months;
7. prior allogeneic bone marrow transplantation or solid organ transplantation;
8. Failure to recover from adverse effects of prior therapy to a CTCAE 5.0 grade score
of ≤ grade 1, excluding alopecia areata;
9. Major surgery within 4 weeks prior to the first dose of study drug or expected to
undergo major surgery during the study period;
10. Patients who have received prior CD47 or SIRpa-targeted therapy;
11. have received any live or attenuated vaccine within 28 days prior to the first dose
of study drug;
12. have received oral or intravenous antibiotics (including antifungals) 2 weeks prior
to the first dose of study drug, except for those who require prophylactic
anti-infective therapy (to prevent urinary tract infections or exacerbations of
chronic obstructive pulmonary disease);
13. Subjects requiring treatment with systemic corticosteroids (dose equivalent to >10
mg prednisone/day) or other immunosuppressive medications within 14 days prior to
the first dose of study drug or during the study period; enrollment is permitted
under the following conditions:
- Use of topical topical or inhaled glucocorticoids;
- Short-term (≤ 7 days) use of glucocorticoids for prophylaxis or treatment of
non-autoimmune allergic diseases;
- Corticosteroids for the replacement therapy of adrenal insufficiency;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital Chinese Academy of Medical Sciense
Address:
City:
Beijing
Country:
China
Start date:
May 28, 2020
Completion date:
December 30, 2024
Lead sponsor:
Agency:
Hangzhou Hanx Biopharmaceuticals, Ltd.
Agency class:
Industry
Source:
Hangzhou Hanx Biopharmaceuticals, Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05731752
