A Study of F0002-ADC in Chinese Patients With Refractory or Recurrent CD30+ Hematologic Malignancies.

Study Overview
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Brief Summary
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This is a Phase I dose escalation study designed to define the maximum tolerable dose(MDT), the safety profile, pharmacokinetic parameters, immunogenicity and anti-tumor activity of F0002-ADC in Chinese patients with relapsed/refractory CD30-positive hematologic malignancies.

Official Title
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A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of F0002-ADC in Chinese Patients With Refractory or Recurrent CD30+ Hematologic Malignancies.

Conditions
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Refractory or Recurrent CD30+ Hematologic Malignancies

Intervention / Treatment
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* Drug: F0002-ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. With relapsed/refractory CD30+ disease that histologically confirmed by central laboratory assessment and pathology review (Priority for cHL, ALCL and MF). Patients must have at least one site of measurable disease by conventional CT scan (defined by unidimensional lymph node lesion ≥ 15 mm or extranodal lesion ≥ 10 mm ), patients with MF, skin nodules can be measured by caliper to meet the criteria as measurable lesions, positive FDG uptake for cHL and ALCL. Patients must have the following required baseline laboratory data: Hb≥80g/L, NEUT≥1.5×109/L, PLT≥75×109/L, TBIL≤1.5 times ULN, ALT/AST≤2.5 times ULN, Cr≤1.25 times ULN or Ccr≥45 ml/min, INR≤1.5 times ULN, APTT≤1.5 times ULN. Patients must be at least 8 weeks apart from the previous autologous stem cell infusion therapy prior to the first dose. Patients must be at least 4 weeks apart from previous radiotherapy, chemotherapy, biologics, immunotherapy, and/or other research-based anticancer therapy prior to the first dose (with nitrogen mustard, melphalan, and nitrosourea for at least 6 weeks). Patients must have a life expectancy > 3 months. Voluntary consent form Exclusion Criteria: Patients who have received an allogeneic stem cell transplant. Patients who have had previous treatment with any anti-CD30 antibody. Patients received antibody therapy 6 weeks or 5 plasma half-life before the first dose. Patients who are receiving other anti-tumor treatments. The toxicity of previous anti-tumor treatment has not recovered to grade 1 or below, except for grade 2 peripheral neurotoxicity and any level of alopecia. Other primary malignant tumors have been seen in the past 3 years (except for cervical cancer in situ or non-melanoma skin cancer or prostate cancer with specific prostate specific antigen). Participants with cardiovascular conditions specified in protocols. NYHA classification grading of cardiac function III/IV. Participants with brain or meningeal disease conditions specified in protocols. Patients with poor diabetes control, High-risk participants with a history of > grade 2 peripheral neuropathy or any active neurologic disease. Patients have psychiatric history. Patients with a history of liver fibrosis or cirrhosis and clinical signs and symptoms suggesting liver fibrosis or cirrhosis. Patients with previous interstitial pneumonia. Patients have active systemic viral, bacterial or fungal infection 4 weeks prior to the first dose HIV antibody positive / HBsAg positive / HCVAb positive. Patients who are allergic to recombinant proteins, murine proteins or to the drug excipients. Patients who are receiving a dose ≥ 20 mg/day of prednisone or glucocorticoid therapy. Female patients who are breastfeeding or pregnant. Patients with fertility who refuses to use contraception during the trial period and within 6 months after the end of the last dose. Other reasons that researchers believe are inappropriate to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: F0002-ADC<br> | Drug: F0002-ADC<br>* Every 21 days for 1 cycle, continue treatment until a maximum 16 cycles. Dose Escalating: 0.3 - 4.8 mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | the maximum tolerable dose | Within 21 days after a single dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Objective response rate | Once every 2 cycles and once every 4 cycles after 4 cycles (each cycle is 21 days), till tumor progression/death /3 years | 
| DOR | Duration of Response | Once every 2 cycles and once every 4 cycles after 4 cycles(each cycle is 21 days), till tumor progression/death /3 years | 
| PFS | Progress Free Survival | Once every 2 cycles and once every 4 cycles after 4 cycles(each cycle is 21 days), till tumor progression/death /3 years | 
| Maximum Plasma Concentration [Cmax] | pharmacokinetic parameter | 1 months after last dose | 
| Area Under the Curve [AUC] | pharmacokinetic parameter | 1 months after last dose | 
| Tmax | pharmacokinetic parameter | 1 months after last dose | 
| Half-life Time [T1/2] | pharmacokinetic parameter | 1 months after last dose | 
| Clearance [CL] | pharmacokinetic parameter | 1 months after last dose | 
| Apparent Volume of Distribution [Vd] | pharmacokinetic parameter | 1 months after last dose | 
| Immunogenicity | Anti-F0002-ADC Antibodies | 1 months after last dose | 
| Incidence of adverse events |  | Till 1 month after last dose | 
| Incidence of laboratory abnormalities |  | Till 1 month after last dose |