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

NCT04357756 | Completed Phase 1

• 1 other identifier: YH001002
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (18)

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

  Up to 1 year

• Steady state AUC

  Up to 1 year

• Maximum serum concentration (Cmax)

  Up to 1 year

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

  Up to 1 year

• Time to reach maximum serum concentration (Tmax)

  Up to 1 year

Study Arms (1)

YH001 combined with Toripalimab

EXPERIMENTAL

All the patients will receive YH001 intravenously as single agent for 21 days followed by combination phase.

Drug: YH001; Drug: Toripalimab

Interventions

YH001 DRUG

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.

YH001 combined with Toripalimab

Toripalimab DRUG

Toripalimab will be administered by intravenously (Q3W) by the fixed dose of 240 mg from the 2nd cycle to 5th cycle.

YH001 combined with Toripalimab

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

Blacktown Hospital, Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

MeSH Terms

Interventions

toripalimab

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 22, 2020
• Study Start: April 21, 2020
• Primary Completion: October 19, 2022
• Study Completion: October 19, 2022
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

AU (3)