A Phase 1, First-in-human (FIH),Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of XKH002 in Patients With Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- XKH002 Injection
- Conditions
- Advanced or Metastatic Solid Tumors
- Sponsor
- Zhejiang Kanova Biopharmaceutical Co., LTD
- Enrollment
- 110
- Locations
- 1
- Primary Endpoint
- maximum tolerated dose (MTD) or the maximum administered dose (MAD) and the recommended dose for expansion (RDE)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, first-in-human (FIH), open-label, multicenter, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of XKH002 in patients with advanced or metastatic solid tumors.
Detailed Description
Overall Study Design: This is a Phase 1, first-in-human (FIH), open-label, multicenter, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of XKH002 in patients with advanced or metastatic solid tumors. The study will include 2 parts, dose escalation and dose expansion Part 1: Dose Escalation Based on the results of previous non-clinical efficacy and toxicology experiments and the prediction of human PK, the initial dose was set at 0.3 mg/kg, and the dose was increased according to 5 dose groups: The 0.3, 1.0, 3.0, 10,20 mg/kg dose-escalation phase will include accelerated titration and a traditional 3+3 dose-escalation design, with 16-30 participants expected to participate in the study. The MTD or MAD will be identified, and all the available PK, PD, tolerability and activity in addition to safety data will be evaluated to select the recommended dose for expansion (RDE). Part 2: Dose Expansion Based on the results of the dose-escalation trial (safety/tolerability, initial efficacy, PK/PD, etc.), it is expected that 20 to 80 participants will be enrolled in the study by RDE dose expansion of monotherapy for selected subjects of 1 to 4 tumor types. Number of Participants: Approximately 16 to 30 patients will be enrolled in Part 1 (dose escalation). Approximately 20 to 80 patients will be enrolled in Part 2 (dose expansion).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 years or older;
- •Life expectancy at least 3 months.
- •Histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumor. Patient has had disease progression on one or more standard treatment regimens, or could not tolerate the treatment, or has no available treatment options.
- •4 The physical status score of "Eastern Cancer Collaboration Group (ECOG)" (see Appendix 5) was 0-1;
- •5 According to RECIST v1.1, all patients must have at least one evaluable lesion at baseline.
- •6 For patients with stable BMS, all of the following criteria must be met:
- •At least 28 days after receiving specialist treatment for central nervous system disorders and at least 14 days after the last corticosteroid treatment.
- •Clinical symptoms were stable after the last treatment: no new central nervous system metastases or radiotherapy complications.
- •Note: Patients who developed new progressive clinical symptoms or spinal cord compression or pIA disease after the last treatment were excluded.
- •7 Laboratory test results during the screening period meet all of the following criteria:
Exclusion Criteria
- •1 The presence or history of any of the following:
- •Current or past autoimmune diseases or immunodeficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions (see Appendix 4) :
- •Patients with autoimmune related hypothyroidism who only need thyroid hormone replacement therapy are eligible to participate in the study;
- •Patients with type 1 diabetes who receive insulin therapy for stable control are eligible to participate in the study;
- •Patients with only dermatologic clinical manifestations of eczema, psoriasis, chronic lichen simple or vitiligo (e.g., excluding psoriatic arthritis) are eligible to participate in the study if they meet all of the following criteria:
- •The skin rash area must be \< 10% of the body surface area;
- •Good disease control at baseline, requiring only inefficient local glucocorticoid therapy;
- •There has been no acute exacerbation of the pre-existing condition requiring psoralen plus A-band ultraviolet radiation, methotrexate, retinoic acid, biologics, oral calcineurin inhibitors, or highly effective or oral glucocorticoid therapy in the past 12 months.
- •2.Known allergy to any component of XKH002;
- •3 Subjects who had major surgery or were scheduled for surgery for any reason within the 4 weeks prior to screening or who the investigator felt might need surgery.
Arms & Interventions
XKH002
A total of 5 dose cohorts will be enrolled and treated: 0.3, 1.0, 3.0, 10, and 20 mg/kg. The dose-escalation process will utilize both the accelerated titration and the conventional 3+3 methods.
Intervention: XKH002 Injection
Outcomes
Primary Outcomes
maximum tolerated dose (MTD) or the maximum administered dose (MAD) and the recommended dose for expansion (RDE)
Time Frame: 24months
To determine the maximum tolerated dose (MTD) or the maximum administered dose (MAD) and the recommended dose for expansion (RDE) of XKH002 in patients with advanced solid tumors
safety and tolerability
Time Frame: 24months
Incidence of treatment emergent adverse events (TEAEs), abnormal clinical laboratory tests, vital signs, electrocardiogram (ECG), and physical examination
Secondary Outcomes
- pharmacokinetic (PK) parameters4(24months)
- immunogenicity(24months)
- antitumor activity1(24months)
- antitumor activity2(24months)
- antitumor activity4(24months)
- antitumor activity5(24months)
- pharmacokinetic (PK) parameters3(24months)
- pharmacokinetic (PK) parameters5(24months)
- pharmacokinetic (PK) parameters1(24months)
- pharmacokinetic (PK) parameters2(24months)
- antitumor activity3(24months)
- pharmacokinetic (PK) parameters6(24months)