This is a 2-part study. Part 1/Phase 1 of the study will be conducted to determine the safety and tolerability of CHO-H01 in subjects with relapsed/refractory CD20+ non-Hodgkin's lymphoma. It will also determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Part 2/Phase 2a will assess the anticancer activity and safety of CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20+ non-Hodgkin's lymphoma.
Phase I FIH study includes subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma, who may benefit from treatment with CHO-H01. In Phase I of the study, the first 2 cohorts will follow a 2-step modified accelerated titration dose escalation design and subsequent cohorts will follow a standard 3+3 dose escalation design. The investigational medicinal product, CHO-H01, will be administered via IV infusion once weekly for 4 weeks in Cycle 1 and then once only (on Day 1) in each subsequent 21-day cycle until disease progression or for up to 6 cycles (19 weeks) of treatment. Once the MTD/RP2D has been confirmed, Phase IIa of the study will be initiated. The purpose of Phase IIa is to assess anticancer activity and safety of CHO-H01 plus lenalidomide in low-grade relapsed/refractory CD20 + non Hodgkin's lymphoma, including follicular lymphoma (Grades 1-3a), marginal zone lymphoma, and small lymphocytic lymphoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Phase 1: Subjects will be administered intravenous (IV) infusion of assigned dose level of CHO-H01, once a week for 4 weeks (Cycle 1-28-Day cycle). From Cycle 2 onwards, on Day 1 of each subsequent 21-day cycle until disease progression (or a total of 6 cycles \[19 weeks\] of study).
Subjects will be administered intravenous (IV) infusion of RP2D level of CHO-H01, once a week for 4 weeks (Cycle 1-28-Day cycle). From Cycle 2 onwards, on Day 1 of each subsequent 28-day cycle until disease progression (or a total of 6 cycles \[19 weeks\] of study).
Subjects will receive oral lenalidomide 20 mg once daily from Day 1 to Day 21 per 28-day cycle.
Tri-Service General Hospital - Neihu Branch - Hematology
Taipei, Taipei, Taiwan
Taipei Medical University - Shuang Ho Hospital - Oncology
New Taipei City, Taipei Special Municipality, Taiwan
National Taiwan University Hospital Yunlin Branch
Huwei, Taiwan, Taiwan
Chi-Mei Medical Center
Tainan, Taiwan, Taiwan
Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology
Taoyuan, Taoyuan, Taiwan
Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
Kaohsiung City, Taiwan
China Medical University Hospital - Hematology/Oncology - Taichung
Taichung, Taiwan
National Cheng Kung University Hospital - Internal Medicine
Tainan, Taiwan
National Taiwan University Hospital - Hematology And Oncology
Taipei, Taiwan
Number of subjects with adverse events (AE)
To assess the safety and tolerability of CHO-H01 as a single agent in subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma and CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20 + non-Hodgkin's lymphoma.
Time frame: Through study completion, approximately 16 months
Number of subjects with dose-limiting toxicities
All AEs and toxicities are evaluated based on the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 5.0. The 5 general grades are Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, and Grade 5: Death (outcome of AE).
Time frame: Through study completion, approximately 16 months
Objective Response Rate
Objective response rate (ORR) is the proportion of subjects with a best overall response of complete response (CR) or partial response (PR). ORR will be measured based on Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Best overall response
The best overall response (CR, PR, stable disease \[SD\], or progressive disease \[PD\]) is defined as the best response across all time points.
Time frame: Through study completion, approximately 16 months
Serum concentration of CHO-HO1
To characterize the PK of CHO-H01.
Time frame: Through study completion, approximately 16 months
Serum Antidrug antibody (ADA) concentration
To investigate the immunogenicity of CHO-H01 alone and in combination with lenalidomide, using a validated bridging ADA assay.
Time frame: Through study completion, approximately 16 months
Clinical benefit rate
The clinical benefit rate (CBR) is the proportion of subjects who achieve CR, PR, and durable SD (SD ≥12 weeks) based on the Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Time to event endpoints of time to progression (TTP)
Time to progression is the time from the date of first study dose to disease progression, evaluated using Modified (not using PET imaging)Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Duration of stable disease
Duration of SD defined as the time interval, in the absence of either CR or PR, will be calculated between the date of the first CHO-H01 administration and the date of disease progression or death for any cause, whichever occurs earlier; based on the Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Progression-free survival
Progression-free survival (PFS) is the time from the date of first study dose to disease progression or death whichever occurs first in subjects, evaluated using Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Duration of response
Duration of response for responders (CR or PR) is the time interval between the date of the earliest qualifying response and the date of disease progression or death for any cause, whichever occurs earlier; based on the Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
Overall survival
The overall survival (OS) is the time from the date of the first study dose to the date of death (any cause), evaluated using Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Time frame: Through study completion, approximately 16 months
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