A Phase 1, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Evidence of Antitumor Activity of ZZ06 in Adult Patients With Advanced Solid Tumor Malignancies
Overview
- Phase
- Phase 1
- Intervention
- ZZ06
- Conditions
- Advanced EGFR Positive Solid Tumor
- Sponsor
- Changchun Intellicrown Pharmaceutical Co. LTD
- Enrollment
- 60
- Locations
- 5
- Primary Endpoint
- Incidence of abnormal physical exam findings
- Status
- Recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This is a Phase 1, Multicenter, Open-label study to assess the safety, tolerability and preliminary efficacy of ZZ06 in participants with all Adult Patients with Advanced EGFR-positive Solid Tumor Malignancies who are not able to have current standard anti-tumor therapies. The purpose of this study is to determine the maximum tolerated dose (MTD) , to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of ZZ06 as a single agent in adult participants with advanced solid tumors.
Detailed Description
The study will start with an accelerated-titration dose escalation scheme, enrolling 1 patient per cohort for the first 2 cohorts with expansion to 3 patients in the event of Grade ≥ 2 treatment-emergent adverse event (TEAE) or dose limiting toxicity (DLT) possibly, probably, or definitely related to the study drug. After the first 2 cohorts, the study will then proceed to a 3+3 design, with enrollment of 3 patients per cohort and expansion to 6 patients in the event of a DLT.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with histologically or cytologically confirmed advanced solid tumor that is positive for EGFR and has progressed despite standard therapy or for whom no standard therapy exists.
- •Patients are required to have archival tumor tissue available for assessment of EGFR status via FDA-approved EGFR assay .
- •Age ≥ 18 years.
- •Patients must have at least 1 measurable lesion as defined by RECIST v1.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Life expectancy ≥ 12 weeks.
- •Baseline organ function and laboratory data meet the following criteria:
- •Bone marrow： ANC ≥ 1500 cells/mm3； Platelet count ≥ 75 000 cells/mm3； Hemoglobin ≥ 8.0 g/dL.
- •Coagulation： Prothrombin time ≤ 1.5× ULN； Activated partial thromboplastin time ≤ 1.5× ULN；
- •Renal function： Serum creatinine ≤ 1.5× ULN ； estimated glomerular filtration rate≥ 60 mL/min (Cockcroft-Gault formula).
Exclusion Criteria
- •History of another primary cancer ≤ 3 years, with the exception of completely resected nonmelanoma skin cancer or carcinoma in situ of uterine cervix.
- •Active or symptomatic CNS metastases. Patients with treated CNS metastases that have been stable for ≥ 4 weeks and do not require treatment with steroids or anticonvulsants may be enrolled at the discretion of the Investigator.
- •Tests positive for hepatitis C virus, hepatitis B virus, or human immunodeficiency virus infection.
- •Active, clinically significant infections.
- •Clinically significant cardiovascular disease, including any of the following:
- •Congestive heart failure (New York Heart Association Class \> 2).
- •Serious cardiac arrhythmia.
- •Myocardial infarction ≤ 6 months.
- •Unstable angina.
- •Prior clinically significant allergic reaction to chimerized or murine monoclonal antibody therapy.
Arms & Interventions
ZZ06 0.03 mg/kg dose group
ZZ06 0.03 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 0.06 mg/kg dose group
ZZ06 0.06 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 0.12 mg/kg dose group
ZZ06 0.12 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 0.22 mg/kg dose group
ZZ06 0.22 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 0.39 mg/kg dose group
ZZ06 0.39 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 0.70 mg/kg dose group
ZZ06 0.70 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
ZZ06 1.00 mg/kg dose group
ZZ06 1.00 mg/kg will be administered twice weekly.A cycle is defined as continuous treatment for 28 days, and the initial treatment course is 2 cycles. Patients can receive up to 6 additional cycles unless disease progression, unacceptable toxicity, or other protocol specified stopping criteria occur. After 6 cycles, additional cycles may be given upon request by the Investigator and approval by the Medical Monitor.
Intervention: ZZ06
Outcomes
Primary Outcomes
Incidence of abnormal physical exam findings
Time Frame: up to 36 weeks
The data of the physical examinations is collected and analyzed according to the time point of the test flow chart
ZZ06 AEs
Time Frame: up to 36 weeks
Adverse events will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
Incidence of abnormal laboratory test results
Time Frame: up to 36 weeks
The data of the clinical laboratory evaluation is collected and analyzed according to the time point of the test flow chart
Secondary Outcomes
- PK parameters: Vz(up to 28 weeks)
- PK parameters: Cmax(up to 28 weeks)
- PK parameters: t1/2(up to 28 weeks)
- PK parameters: Clearance rate (CL)(up to 28 weeks)
- PK parameters: Area under curve (AUC)(up to 28 weeks)