A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies
- Registration Number
- NCT04353102
- Lead Sponsor
- Eucure (Beijing) Biopharma Co., Ltd
- Brief Summary
This is an open-label, dose-escalation study of the study drug YH002. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of YH002 in patients with advanced solid Malignancies
- Detailed Description
This is a single arm clinical trial in subjects with advanced solid tumor receiving multiple doses of YH002 intravenously (IV). YH002 will be administered (IV) in 6-48 patients with advanced solid tumors. An accelerated titration method followed by a traditional 3+3 dose escalation algorithm will be utilized to determine MTD/MAD. Patients will be dosed at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H every 3 weeks (Q3W).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description YH002 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.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) Cycle 1 of each cohort. Duration of one cycle is 3 weeks 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
Dose-limiting toxicities (DLT) Cycle 1 of each cohort. Duration of one cycle is 3 weeks DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)
Number of participants with adverse events and serious adverse events From screening up to 2 year 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
- Secondary Outcome Measures
Name Time Method Area under the serum concentration versus time curve within one dosing interval (AUCtau) Up to 2 years To determine the pharmacokinetics (PK) profile of YH002
Volume of distribution at steady state (Vss) Up to 2 years To determine the pharmacokinetics (PK) profile of YH002
Time to reach maximum serum concentration (Tmax) Up to 2 years To determine the PK profile of YH002
Dose proportionality Up to 2 years To determine the PK profile of YH002
Disease control rate (DCR) Up to 2 years To assess the preliminary antitumor activity of YH002
Duration of disease control (DOC) Up to 2 years To assess the preliminary antitumor activity of YH002
Trough concentration before the next dose is administered (Ctrough) Up to 2 years To determine the PK profile of YH002
Terminal half-life (T1/2) Up to 2 years To determine the PK profile of YH002
Incidence of anti-drug antibodies (ADAs) Up to 2 years To assess the immunogenicity of YH002
Volume of distribution (Vd) Up to 2 years To determine the pharmacokinetics (PK) profile of YH002
Clearance (CL) Up to 2 years To determine the PK profile of YH002
Incidence of neutralizing antibodies (NAbs) Up to 2 years To assess the immunogenicity of YH002
Objective response rate (ORR) Up to 2 years To assess the preliminary antitumor activity of YH002
Progression free survival (PFS) Up to 2 years To assess the preliminary antitumor activity of YH002
Time to response (TTR) Up to 2 years To assess the preliminary antitumor activity of YH002
Maximum serum concentration (Cmax) Up to 2 years To determine the PK profile of YH002 as single agent
Duration of response (DOR) Up to 2 years To assess the preliminary antitumor activity of YH002
Trial Locations
- Locations (3)
St George Private Hospital
🇦🇺Kogarah, New South Wales, Australia
Macquarie University
🇦🇺Macquarie, New South Wales, Australia
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia