A Study to Evaluate the Safety, Tolerability and How YH002 Enters, Moves Through and Exits the Body in Subjects With Advanced Solid Malignancies

NCT04353102 | Completed Phase 1 DMC

• 1 other identifier: YH002002
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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

Conditions

Advanced Solid Malignancies

Keywords

dose escalation; safety; tolerability; advanced solid malignancie; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Number of participants with adverse events and serious adverse events

  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

  From screening up to 2 year

• Maximum tolerated dose (MTD)

  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

  Cycle 1 of each cohort. Duration of one cycle is 3 weeks

• Dose-limiting toxicities (DLT)

  DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)

  Cycle 1 of each cohort. Duration of one cycle is 3 weeks

Secondary Outcomes (17)

• Area under the serum concentration versus time curve within one dosing interval (AUCtau)

  Up to 2 years

• Volume of distribution (Vd)

  Up to 2 years

• Volume of distribution at steady state (Vss)

  Up to 2 years

• Maximum serum concentration (Cmax)

  Up to 2 years

• Trough concentration before the next dose is administered (Ctrough)

  Up to 2 years

Study Arms (1)

YH002

EXPERIMENTAL

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.

Drug: YH002

Interventions

YH002 DRUG

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.

YH002

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eucure (Beijing) Biopharma Co., Ltd: lead

Study Sites (3)

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Macquarie University

Macquarie, New South Wales, 2162, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 20, 2020
• Study Start: April 22, 2020
• Primary Completion: September 14, 2021
• Study Completion: November 24, 2021
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

AU (3)