Clinical trial NCT04353102: A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Malignancies
Keywords: dose escalation
safety
tolerability
advanced solid malignancie
pharmacokinetics
Lead sponsor: Eucure (Beijing) Biopharma Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-04-20
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: From screening up to 2 year
measure: Maximum tolerated dose (MTD)
timeFrame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
measure: Dose-limiting toxicities (DLT)
timeFrame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
Secondary outcomes:
measure: Area under the serum concentration versus time curve within one dosing interval (AUCtau)
timeFrame: Up to 2 years
measure: Volume of distribution (Vd)
timeFrame: Up to 2 years
measure: Volume of distribution at steady state (Vss)
timeFrame: Up to 2 years
measure: Maximum serum concentration (Cmax)
timeFrame: Up to 2 years
measure: Trough concentration before the next dose is administered (Ctrough)
timeFrame: Up to 2 years
measure: Time to reach maximum serum concentration (Tmax)
timeFrame: Up to 2 years
measure: Clearance (CL)
timeFrame: Up to 2 years
measure: Terminal half-life (T1/2)
timeFrame: Up to 2 years
measure: Dose proportionality
timeFrame: Up to 2 years
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Up to 2 years
measure: Incidence of neutralizing antibodies (NAbs)
timeFrame: Up to 2 years
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Progression free survival (PFS)
timeFrame: Up to 2 years
measure: Time to response (TTR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of disease control (DOC)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Macquarie
country: Australia
facility: Macquarie University
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
Study officials:
References: