Study on the Tolerability and Pharmacokinetics of HX009 in Patients With Advanced Solid Tumors

NCT05731752 | Active Not Recruiting Phase 1

• 1 other identifier: HX009-I-01(CN)
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (3)

• In phase Ia: Incidence of Dose Limiting Toxicities (DLT) of HX009 in patients with advanced solid tumors

  Adverse events (AEs) determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).

  At the end of Cycle 2 (each cycle is 14 days)

• Incidence of adverse events (AE) of HX009 in patients with advanced solid tumors

  Adverse events (AEs) determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).

  Collected adverse events from signing of informed consent through at least 28 days after the end of treatment, or until other cancer treatment regimens have been started (whichever occurs earlier).

• In phase IB:Incidence of Dose Limiting Toxicities (DLT) in HX009 in patients with advanced solid tumors

  Incidence and severity of adverse events as assessed by the investigator according to RECIST 1.1;

  At the end of Cycle 2 (each cycle is 14 days)

Secondary Outcomes (13)

• In Phase Ia: Pharmacokinetics (PK): Maximum plasma concentration of drug (Cmax)

  At Cycle 1 ,Cycle 6 and Cycles 2 -5 (each cycle is 14 days)

• Pharmacokinetics (PK): Time to reach Cmax (Tmax)

  At Cycle 1 ,Cycle 6 and Cycles 2 -5(each cycle is 14 days)

• Terminal Half-life （t½）of HX009

  At Cycle 1 ,Cycle 6 and Cycles 2 -5 (each cycle is 14 days)

• Area Under the Serum Concentration-time Curve (AUC)

  At Cycle 1 ,Cycle 6 and Cycles 2 -5 (each cycle is 14 days)

• Number of Participants With Positive Anti-Drug Antibody (ADA) of HX009

  At Cycles 1-6, 9, 13, 17, and then every 8 cycles up to approximately 1 years: within 1 hour before infusion (each cycle is 14 days).

Study Arms (1)

HX009

EXPERIMENTAL

Study treatment: HX009 administered every 2 weeks (14 \[±3\] days) via intravenous infusion.

Drug: HX009

Interventions

HX009 DRUG

The subjects will receive HX009 treatment via IV infusion once every 2 weeks at different dose escalation cohorts

Also known as: Recombinant humanized anti-CD47/PD-1 bifunctional antibody

HX009

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In Phase Ia.
• Subjects must meet all of the following enrollment criteria to be enrolled in this study:
• Voluntarily sign an informed consent form, understand the study and be willing to follow and be capable of completing all trial procedures;
• Male or female, age 18-70 years (including borderline values);
• ECOG score: 0 to 1;
• 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;
• 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;
• Expected survival ≥ 12 weeks;
• 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;
• 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;
• Have appropriate organ and hematopoietic function and no severe cardiac, pulmonary, hepatic, or renal dysfunction or immunodeficiency based on the following laboratory tests

You may not qualify if:

• in Phase Ia:
• Subjects with any of the following are not eligible for enrollment in this study:
• 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;
• 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;
• 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 :
• Subjects with any of the following are not eligible for enrollment in this study:
• Histologic or pathologic diagnosis of choroidal malignant melanoma;
• 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.
• 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);

Sponsors & Collaborators

• Hangzhou Hanx Biopharmaceuticals, Ltd.: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciense

Beijing, China

Location

Study Design

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

Study Record Dates

• First Submitted: January 29, 2023
• First Posted: February 16, 2023
• Study Start: May 28, 2020
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)