The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies

NCT04097769 | Completed Phase 1 DMC

• 1 other identifier: HX009-I-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. The study will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and to evaluate the preliminary antitumor activity of HX009.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Adverse Events (AEs)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product.

  All AEs up to 90 days after the last dose of study drug

• Number of Participants With Dose-Limiting Toxicities (DLT) of HX009

  Severity of adverse events (AEs) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For the purpose of dose escalation, any of the following AEs occurring during the DLT observation period that were attributable to one or both study drugs were classified as DLTs.

  At the end of Cycle2(each cycle is 14 days)

Secondary Outcomes (5)

• Time for Cmax (Tmax) of HX009

  Approximately 2 years

• Terminal Half-life （t½）of HX009

  Approximately 2 years

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

  Approximately 2 years

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

  Cycles 1, 2, 3, 4, 5, 6, 7, 9, 13, and 17, and then every 8 cycles, Day 1: within 60 minutes before the start of the infusion(each cycle is 14 days)

• Objective response rate(ORR) Per Investigator Assessment Using RECIST 1.1

  Approximately 2 years

Study Arms (1)

HX009

OTHER

Study treatment: HX009 administered every 2 weeks (14 \[±1\] days) via intravenous infusion.

Drug: HX009

Interventions

HX009 DRUG

During study treatment, subjects will receive HX009 treatment via IV infusion once every 2 weeks at doses of 0.1, 0.3, 1, 2, 3, 5, and 7.5 mg/kg.

Also known as: anti-PD-1/CD47 infusion protein

HX009

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject aged 18 to 70 years, inclusive.
• Eastern Cooperative Oncology Group performance status of 0 to 1.
• Histologically confirmed advanced malignant tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
• At least 1 measurable tumor according to RECIST v1.1 (see Appendix 7 of the protocol).
• Life expectancy ≥12 weeks.
• A subject with a history of brain/meninges metastases who has received prior topical treatment (surgery/radiotherapy) before the start of the study and is clinically stable for at least 3 months is allowed (prior treatment with corticosteroids is permitted; however, if a subject requires systemic concomitant treatment with corticosteroids, they must be excluded).
• Adequate organ function, as indicated by the following laboratory values, within 14 days before signing informed consent:
• Hematology
• Hemoglobin ≥100 g/L (no blood transfusion is allowed within 14 days before signing informed consent)
• Absolute neutrophil count ≥1.5 × 109/L
• Platelet count ≥100 × 109/L Biochemistry
• Total bilirubin ≤1.5 × upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (ALT and AST ≤5 × ULN for subjects with liver metastases)
• Serum creatinine ≤1 × ULN
• Prothrombin time/international normalized ratio ≤1.5 × ULN or activated partial thromboplastin time ≤1.5 × ULN (for subjects on anticoagulants, prothrombin time or activated partial thromboplastin time must be within the normal range for anticoagulants).

You may not qualify if:

• For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4):
• Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4, CD47, or any other immunotherapy or immune-oncology agent within 4 weeks of the first dose study treatment
• Subjects must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy
• Any adverse events reported while receiving prior immunotherapy must have completely resolved or resolved to Grade 1 prior to screening for this study.
• Prior malignancy active within the previous 2 years except for the tumor for which a subject is enrolled in the study and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
• Allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their components.
• Receipt of any immunotherapy, or investigational anticancer therapy within 4 weeks prior to the first dose of study treatment; in the case of mAbs (for investigational use or immunotherapy), 6 weeks prior to the first dose of study treatment.
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy (except for subjects with metastatic prostate cancer on androgen deprivation treatment eg, goserelin, leuprorelin) for cancer. Concurrent use of hormones for noncancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable. NOTE: Local treatment of isolated lesions for palliative intent is acceptable (eg, by local surgery or local radiotherapy).
• Radiation therapy (localized radiation therapy for therapeutic purpose is allowed) within 4 weeks of the first dose of study treatment.
• Female subject who is pregnant or lactating.
• Tests positive for human immunodeficiency virus, or has active hepatitis B virus or hepatitis C virus.
• Active, or history of, autoimmune disease (within the past 2 years) that may recur (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc) or are at high risk (eg, receiving an immunosuppressive treatment for an organ transplant); however, subjects with the following are allowed to enroll:
• Type I diabetes that is stable after a fixed dose of insulin
• Only requiring hormone replacement therapy for autoimmune hypothyroidism
• Skin disease that does not require treatment such as eczema, rash that accounts for \<10% of the body surface, psoriasis without ophthalmic symptoms.

Sponsors & Collaborators

• Waterstone Hanxbio Pty Ltd: lead

Study Sites (1)

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Study Officials

• Paul de Souza

  St George Private Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: HX009

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: September 20, 2019
• Study Start: June 12, 2019
• Primary Completion: March 18, 2021
• Study Completion: September 29, 2022
• Last Updated: December 12, 2022

Record last verified: 2022-12

Locations

AU (1)