Clinical trial NCT04357756: A Study to Assess YH001 in Combination With Toripalimab Injection in Subjects With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: dose escalation
safety
tolerability
advanced solid tumors
pharmacokinetics
Lead sponsor: Eucure (Beijing) Biopharma Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-04-22
Enrollment: 29
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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: From screening up to 1 year
measure: Maximum tolerated dose (MTD)
timeFrame: During Cycle 1 (each cycle is 21 days)
measure: Dose-limiting toxicities (DLT)
timeFrame: During Cycle 1 (each cycle is 21 days)
Secondary outcomes:
measure: Area under the serum concentration versus time curve within one dosing interval (AUCtau)
timeFrame: Up to 1 year
measure: Steady state AUC
timeFrame: Up to 1 year
measure: Maximum serum concentration (Cmax)
timeFrame: Up to 1 year
measure: Trough concentration before the next dose is administered (Ctrough)
timeFrame: Up to 1 year
measure: Time to reach maximum serum concentration (Tmax)
timeFrame: Up to 1 year
measure: Clearance (CL)
timeFrame: Up to 1 year
measure: Volume of distribution (Vd)
timeFrame: Up to 1 year
measure: Terminal half-life (T1/2)
timeFrame: Up to 1 year
measure: Dose proportionality
timeFrame: Up to 1 year
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Up to 1 year
measure: Incidence of neutralizing antibodies (NAbs)
timeFrame: Up to 1 year
measure: Objective response rate (ORR)
timeFrame: Up to 1 year
measure: Duration of response (DOR)
timeFrame: Up to 1 year
measure: Time to response (TTR)
timeFrame: Up to 1 year
measure: Progression free survival (PFS)
timeFrame: Up to 1 year
measure: Overall survival (OS)
timeFrame: Up to 1 year
measure: Disease control rate (DCR)
timeFrame: Up to 1 year
measure: Duration of disease control (DDC)
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital, Blacktown Cancer and Haematology Centre
state: New South Wales
city: Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
Study officials:
References: