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

• ClinicalTrials.gov Identifier: NCT04353102
• Recruitment Status: Completed
• First Posted: April 20, 2020
• Last Update Posted: July 22, 2022
• Sponsor: Eucure (Beijing) Biopharma Co., Ltd
• Information provided by (Responsible Party): Eucure (Beijing) Biopharma Co., Ltd

Study Description

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

Condition or disease	Intervention/treatment	Phase
Advanced Solid Malignancies	Drug: YH002	Phase 1

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 22, 2020
• Actual Primary Completion Date: September 14, 2021
• Actual Study Completion Date: November 24, 2021

Arms and Interventions

Arm

Intervention/treatment

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.

Drug: YH002; 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.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events and serious adverse events [ Time Frame: 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
2. Maximum tolerated dose (MTD) [ Time Frame: 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
3. Dose-limiting toxicities (DLT) [ Time Frame: 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 Outcome Measures :

1. Area under the serum concentration versus time curve within one dosing interval (AUCtau) [ Time Frame: Up to 2 years ]
   To determine the pharmacokinetics (PK) profile of YH002
2. Volume of distribution (Vd) [ Time Frame: Up to 2 years ]
   To determine the pharmacokinetics (PK) profile of YH002
3. Volume of distribution at steady state (Vss) [ Time Frame: Up to 2 years ]
   To determine the pharmacokinetics (PK) profile of YH002
4. Maximum serum concentration (Cmax) [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002 as single agent
5. Trough concentration before the next dose is administered (Ctrough) [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002
6. Time to reach maximum serum concentration (Tmax) [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002
7. Clearance (CL) [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002
8. Terminal half-life (T1/2) [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002
9. Dose proportionality [ Time Frame: Up to 2 years ]
   To determine the PK profile of YH002
10. Incidence of anti-drug antibodies (ADAs) [ Time Frame: Up to 2 years ]
    To assess the immunogenicity of YH002
11. Incidence of neutralizing antibodies (NAbs) [ Time Frame: Up to 2 years ]
    To assess the immunogenicity of YH002
12. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002
13. Duration of response (DOR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002
14. Progression free survival (PFS) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002
15. Time to response (TTR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002
16. Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002
17. Duration of disease control (DOC) [ Time Frame: Up to 2 years ]
    To assess the preliminary antitumor activity of YH002

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, New South Wales

St George Private Hospital

Kogarah, New South Wales, Australia, 2217

Macquarie University

Macquarie, New South Wales, Australia, 2162

Australia, Victoria

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia, 3199

Sponsors and Collaborators

Eucure (Beijing) Biopharma Co., Ltd

More Information

• Responsible Party: Eucure (Beijing) Biopharma Co., Ltd
• ClinicalTrials.gov Identifier: NCT04353102
• Other Study ID Numbers: YH002002
• First Posted: April 20, 2020
• Last Update Posted: July 22, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eucure (Beijing) Biopharma Co., Ltd:

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

Additional relevant MeSH terms:

Neoplasms