YH004 is a humanized monoclonal antibody that specifically binds to 4-1BB, and acts as an agonist against 4-1BB. This first in human study of YH004 is designed to establish the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D) of YH004, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody (Toripalimab) in the treatment of advanced solid tumors and relapsed or refractory non-Hodgkin Lymphoma.
This is an open-label, non-randomized, two-stage, FIH Phase 1 study, utilizing an accelerated dose escalation followed by a traditional 3 + 3 dose escalation algorithm to identify the MTD and/or RP2D of YH004 as a single agent (monotherapy) and in combination with Toripalimab. The first stage of the study is the dose escalation phase (i.e., Phase 1a). The second stage of the study is the dose expansion phase (i.e., Phase 1b). During the study, dose interruption(s) and/or delay(s) may be implemented based on toxicity. Dose modifications are permitted following protocol guidelines. Intra-patient dose escalations will be allowed for the early dose cohorts (single-patient dose groups) in Phase 1a. Patients will be considered evaluable for safety and tolerability if they receive at least one dose of YH004 or Toripalimab at the specified cohort dose. Patients in all parts of the trial will remain on therapy until confirmed disease progression or for 1 year, whichever occurs first. However, patients who are clinically unstable will discontinue following the initial assessment of disease progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
IV infusion once every 3 weeks (Q3W).
Cabrini Health Limited
Malvern East, Australia
Westmead Hospital
Sydney, Australia
Southside Cancer Care Centre, School of Medicine, University of Wollongong
Wollongong, Australia
Treatment-emergent adverse events (TEAEs) including determination of DLTs and serious AEs (SAEs)
Adverse events will be assessed, and severity will be assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: up to 24 months
Maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D)
The MTD and/or RP2D will be determined based on TEAEs
Time frame: up to 24 months
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