Advanced Solid Malignancies
Conditions
Keywords
dose escalation, safety, tolerability, advanced solid malignancie, pharmacokinetics
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).
Interventions
DRUGYH002
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.
Sponsors
Eucure (Beijing) Biopharma Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal half-life (T1/2) | Up to 2 years | To determine the PK profile of YH002 |
| Dose proportionality | 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 |
| 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 (Vd) | 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 |
| Maximum serum concentration (Cmax) | Up to 2 years | To determine the PK profile of YH002 as single agent |
| 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 |
| Duration of response (DOR) | 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 |
| 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 |
| Time to reach maximum serum concentration (Tmax) | Up to 2 years | To determine the PK profile of YH002 |
| Clearance (CL) | Up to 2 years | To determine the PK profile of YH002 |
Countries
Australia
Outcome results
None listed