A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies
A First-in-Human (FIH), Multicenter, Open-Label, Phase 1 Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of YH002 in Subjects With Advanced Solid Malignancies
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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New South Wales
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Kogarah, New South Wales, Australia, 2217
- St George Private Hospital
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Macquarie, New South Wales, Australia, 2162
- Macquarie University
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Victoria
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Frankston, Victoria, Australia, 3199
- Peninsula & South Eastern Haematology and Oncology Group
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female, aged ≥ 18 years
- Confirmed as histologically or cytologically, locally advanced or metastatic non-resectable solid tumors, must have received and progressed on, or been ineligible for, or intolerant of available standard therapies known to confer clinical benefit or for whom no standard therapy exits
- Subjects enrolled in Dose D, Dose E, Dose F, Dose G, and Dose H cohorts must have at least one measurable lesion per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 and life expectancy no less than 3 months
- Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy
Exclusion Criteria:
- Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS- directed therapy, and do not require corticosteroids or anticonvulsants are eligible for study entry
- Received anticancer therapy or radiation therapy within 5 half-lives or 4 weeks prior to study entry, whichever is shorter
- Received palliative radiotherapy to a single area of metastasis within 2 weeks prior to study entry
- Received agonist antibodies to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies prior to the study entry
- Allergy or sensitivity to YH002, or known allergies to antibodies produced from Chinese hamster ovary cells which assessed to increase the potential for an adverse hypersensitivity to YH002 by Investigator
- History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody
- Grade ≥3 irAEs or irAEs that lead to discontinuation of prior immunotherapy. Hypothyroidism, Type 1 DM, and dermatologic irAEs (except previous Steven Johnson Syndrome, toxic epidermal necrolysis, or other severe forms of dermatitis). Type 1 DM should be controlled with reduction of toxicity to Grade 1 or less
- Concomitant active autoimmune disease or history of autoimmune disease requiring systemic treatment or history of autoimmune disease within 2 years prior to study entry (except vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy)
- Received steroids or other immunosuppressive systemic therapy within 4 weeks prior to the first dose of the study drug, or has need to be treated during the study (except using on low systemic absorption location prevent or treat non- autoimmune condition)
- Active hepatitis B or C. Hepatitis B carriers without active disease or cured Hepatitis C may be enrolled
- Severe cardiovascular disease within 6 months of study entry
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
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Experimental: YH002
All subject will receive YH002 intravenously as single agent every three weeks (Q3W) for up to 2 years, until intolerable toxicity, confirmed disease progression, withdrawal of consent, or Investigator decision, whichever comes first.
Subjects who remain on treatment in the absence of disease progression for more than 2 years may continue to receive study drug through a single patient IND.
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YH002 will be administered intravenously every three weeks (Q3W) for up to 2 years at doses of Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H.
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Maximum tolerated dose (MTD)
Time Frame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
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MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycle
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Cycle 1 of each cohort. Duration of one cycle is 3 weeks
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Dose-limiting toxicities (DLT)
Time Frame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
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DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)
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Cycle 1 of each cohort. Duration of one cycle is 3 weeks
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Number of participants with adverse events and serious adverse events
Time Frame: From screening up to 2 year
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The safety profile of YH002 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
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From screening up to 2 year
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Area under the serum concentration versus time curve within one dosing interval (AUCtau)
Time Frame: Up to 2 years
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To determine the pharmacokinetics (PK) profile of YH002
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Up to 2 years
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Volume of distribution (Vd)
Time Frame: Up to 2 years
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To determine the pharmacokinetics (PK) profile of YH002
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Up to 2 years
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Volume of distribution at steady state (Vss)
Time Frame: Up to 2 years
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To determine the pharmacokinetics (PK) profile of YH002
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Up to 2 years
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Maximum serum concentration (Cmax)
Time Frame: Up to 2 years
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To determine the PK profile of YH002 as single agent
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Up to 2 years
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Trough concentration before the next dose is administered (Ctrough)
Time Frame: Up to 2 years
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To determine the PK profile of YH002
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Up to 2 years
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Time to reach maximum serum concentration (Tmax)
Time Frame: Up to 2 years
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To determine the PK profile of YH002
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Up to 2 years
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Clearance (CL)
Time Frame: Up to 2 years
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To determine the PK profile of YH002
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Up to 2 years
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Terminal half-life (T1/2)
Time Frame: Up to 2 years
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To determine the PK profile of YH002
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Up to 2 years
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Dose proportionality
Time Frame: Up to 2 years
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To determine the PK profile of YH002
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Up to 2 years
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Incidence of anti-drug antibodies (ADAs)
Time Frame: Up to 2 years
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To assess the immunogenicity of YH002
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Up to 2 years
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Incidence of neutralizing antibodies (NAbs)
Time Frame: Up to 2 years
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To assess the immunogenicity of YH002
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Up to 2 years
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Objective response rate (ORR)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Duration of response (DOR)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Progression free survival (PFS)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Time to response (TTR)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Disease control rate (DCR)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Duration of disease control (DOC)
Time Frame: Up to 2 years
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To assess the preliminary antitumor activity of YH002
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Up to 2 years
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Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- YH002002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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