A Study to Assess YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors

A First-in-human (FIH), Open-Label, Phase I Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors

This is an open-label, dose-escalation study of YH001 administered intravenously (IV) in combination with Toripalimab. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of YH001 when administered in combination with Toripalimab to subjects with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: YH001; Drug: Toripalimab

Detailed Description

This trial will have a run-in phase to explore the safety and tolerability of YH001 as a single agent for 21 days as DLT observation period then followed by a combination phase to further explore the safety and tolerability of YH001 combined with Toripalimab (anti-PD-1 antibody) for each dose level during dose escalation.

The dose escalation will follow the traditional "3 + 3" dose escalation scheme. These subjects will be treated with YH001 and Toripalimab. YH001 will be administered intravenously every three weeks (Q3W) for 15 weeks (5 cycles) at doses of Dose A, Dose B, Dose C, Dose D, Dose E, Dose F and Dose G. Toripalimab will be administered by IV (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle. A single subject will be enrolled at Dose A as starting dose of YH001, and subsequent cohort will be expanded to include 3-6 subjects.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital, Blacktown Cancer and Haematology Centre
    • Kogarah, New South Wales, Australia, 2217
      • St George private Hospital
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula & South Eastern Haematology and Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, aged ≥ 18 years
• Have advanced histologically or cytologically confirmed solid tumor
• Have progressed on after treatment with standard therapies or intolerant of standard care
• At least 1 unidimensional measurable target lesion per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
• Have life expectancy of at least 12 weeks based on investigator's judgement

Exclusion Criteria:

• Treated with any investigational drug within 4 weeks prior to the fist dose of study drug
• Received any anticancer therapy less than 28 days prior to the first administration of study drug or within 5 half-lives of the therapy agent, whichever is shorter. Prior palliative radiotherapy to bone metastases ≤ 2 weeks prior to the first dose of YH001 is acceptable
• Subjects with prior anti-CTLA-4 checkpoint inhibitors should be excluded
• Subjects with prior PD-1/L1 treatment intolerate to PD-1/L1 therapy should be excluded
• Subjects with a history of ≥ Grade 3 immune-related adverse events (AEs) resulted from previous immunotherapy or an AE of any grade that resulted in discontinuation of prior immunotherapy
• Subjects with a history of ≥ Grade 2 pneumonitis resulted from previous immunotherapy or with a SpO2 by pulse oximetry < 92% at the screening
• Subjects requiring systemic treatment with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 21 days before the planned first dose of study drug or has need to be treated while on trial. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic, nasal and intra-articular injections of steroids are allowed
• Subjects with concomitant active autoimmune disease, history of autoimmune disease requiring systemic treatment, or history of autoimmune disease within the two years prior to study entry. Exceptions are subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy
• Primary central nervous system (CNS) malignancies or symptomatic CNS metastases. But subjects with asymptomatic CNS metastases might be eligible if they have no clinical evidence of progression since completion of CNS-directed therapy, minimum 4 weeks between completion of radiotherapy and the first dose of YH001 and are currently not receiving corticosteroids
• QTc > 450 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome
• Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ Grade 1 per CTCAE v5.0, except alopecia, < Grade 2 sensory neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YH001 combined with Toripalimab; All the patients will receive YH001 intravenously as single agent for 21 days followed by combination phase.	Drug: YH001; YH001 will be administered intravenously every three weeks (Q3W) for 15 weeks (5 cycles) at doses of Dose A, Dose B, Dose C, Dose D, Dose E, Dose F and Dose G.; Drug: Toripalimab; Toripalimab will be administered by intravenously (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events and serious adverse events	The safety profile of YH001 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 1 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	During Cycle 1 (each cycle is 21 days)
Dose-limiting toxicities (DLT)	DLT is defined as a toxicity (adverse event at least possibly related to YH001) occurring during the DLT observation period (the initial 21 days) both in run-in phase of YH001 as single agent and in combination phase of YH001 in combination with Toripalimab	During Cycle 1 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration versus time curve within one dosing interval (AUCtau)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Steady state AUC	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Maximum serum concentration (Cmax)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Trough concentration before the next dose is administered (Ctrough)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Time to reach maximum serum concentration (Tmax)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Clearance (CL)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Volume of distribution (Vd)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Terminal half-life (T1/2)	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Dose proportionality	To determine the PK profile of YH001 alone and in combination with Toripalimab	Up to 1 year
Incidence of anti-drug antibodies (ADAs)	To assess the immunogenicity of YH001 in combination with Toripalimab	Up to 1 year
Incidence of neutralizing antibodies (NAbs)	To assess the immunogenicity of YH001 in combination with Toripalimab	Up to 1 year
Objective response rate (ORR)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Duration of response (DOR)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Time to response (TTR)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Progression free survival (PFS)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Overall survival (OS)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Disease control rate (DCR)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year
Duration of disease control (DDC)	To assess the preliminary antitumor activity of YH001 in combination with Toripalimab	Up to 1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2020
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 21, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; advanced solid tumors; dose escalation
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: YH001002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No