A Safety Study of YQ23 in Advanced Solid Tumors Patients

NCT04513067 | Terminated Phase 1 DMC

• 1 other identifier: YQ23-19002
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is an early phase dose escalation study which is divided into two stages: (1) Single agent of the test drug YQ23, and (2) in combination with pembrolizumab administered to patients with advanced solid tumors. The purpose of the study is find out the safety and tolerability profile, as well as maximum tolerated dose (MTD) of YQ23 as single agent (stage 1) and in combination with pembrolizumab (stage 2). Stage 2 will start only when the MTD of single agent YQ23 has been established in Stage 1. The distribution of YQ23 in the blood, the tumor response to YQ23 (and pembrolizumab in stage 2), the change of some pre-defined biomarkers in the tumor tissues and blood, and the change of antibody response and its relationship with the disease response, safety and drug level in the blood will also be evaluated. In stage 1, eligible patients will be given intravenous infusion of YQ23 weekly for 6 weeks. In stage 2, eligible patients will be also be given a fixed dose of pembrolizumab 200 mg on Day 1 and every 3 weeks thereafter in addition to the weekly dose of YQ23. Dose escalation decision will be made based on the safety data available for the 6 weeks study treatment(s). Patients may continue study treatment(s) beyond 6 weeks if s/he tolerates the study drug(s) well, the disease does not get worse after first 6 doses and meet all treatment continuation criteria, as judged by the study doctor.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) of YQ23 as single agent (Stage 1) and when in combination with Pembrolizumab (Stage 2)

  The incidence and severity of AEs and SAEs including the following cardiac events of interests evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0: * High-sensitivity cardiac troponin I increase * Ejection fraction decrease * Electrocardiogram corrected QT interval prolongation * Creatine phosphokinase increase

  From start of study until 12 weeks after last dose

• Establishment of MTD for YQ23 as single agent (Stage 1) and when in combination with Pembrolizumab (Stage 2)

  MTD will be evaluated by the incidence of DLT for which it will be determined based on the incidence and intensity of drug-related adverse events (toxicities) occurring up to 8 days after the administration of the fourth dose of YQ23 in the single and combo therapy dose escalations. The toxicities will be graded by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.

  From the start of treatment until Day 6 post Dose 6 of YQ23 at each dose level (in both stages)

Secondary Outcomes (4)

• Pharmacokinetics of YQ23 as measured by plasma concentration in single agent group and combo therapy group

  Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 6

• Pharmacokinetics of YQ23 as measured by area under the plasma concentration-time curve in single agent group and combo therapy group

  Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 6

• Pharmacokinetics of YQ23 as measured by terminal half-life in single agent group and combo therapy group

  Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 6

• Disease control rate (DCR) by YQ23 when given alone and when in combination with pembrolizumab

  This will be measured at Day 6 post YQ23 Dose6

Study Arms (2)

Stage 1: Single agent

EXPERIMENTAL

Intravenous weekly dose of YQ23 for 6 weeks with an ascending dose levels of 20, 30, 60, 90 and 120 mg/kg will be evaluated.

Biological: YQ23

Stage 2: Combination Therapy

EXPERIMENTAL

Intravenous weekly dose of YQ23 for 6 weeks with an ascending dose levels from 20 mg/kg to the MTD obtained from Stage 1 in combination of a fixed dose of 200 mg intravenous pembrolizumab given on the same day following YQ23 administration and every 3 weeks thereafter.

Combination Product: Pembrolizumab

Interventions

YQ23 BIOLOGICAL

YQ23 as a single agent will be given in Stage 1.

Stage 1: Single agent

Pembrolizumab COMBINATION_PRODUCT

Pembrolizumab will be given in combination with YQ23 in Stage 2

Stage 2: Combination Therapy

Eligibility Criteria

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

You may qualify if:

• Females or males age ≥ 18 years at the time of informed consent
• Patients with histologically or cytologically confirmed solid tumors with the potential to benefit from immunotherapy, such as triple negative breast cancer, colorectal cancer, liver cancer, non-small cell lung cancer, or renal cell carcinoma, who have progressed despite prior standard therapy or are intolerant of the standard therapy, or for whom no standard therapy exists. Patients with colorectal cancer should have received prior second-line therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• At least one measurable target lesion as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at baseline
• Must have a site of disease amenable to biopsy and not chosen as target or non-target lesions for tumor response assessment (RECIST 1.1)
• Expected life expectancy of ≥ 12 weeks
• Adequate bone marrow function at screening:
• Hemoglobin \> 8.5 g/dl
• Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L
• Platelet count ≥ 75 x 10\^9/L
• PT-INR \< 1.5 or APTT \< 1.5 x upper limit of normal
• Adequate liver function at screening:
• Total bilirubin ≤ 1.5 x upper limit of normal
• Serum AST and ALT ≤ 2.5 x upper limit of normal
• Adequate renal function at screening:

You may not qualify if:

• Subjects who have received any anti-cancer treatment or investigational agent within 21 days prior to the first dose of the trial treatment
• Any surgery or radiotherapy within 28 days prior to the first dose of the trial treatment
• Any toxic effects (except \<= Grade 2: hair loss, vomiting, nausea, sensory neuropathy, endocrinopathies under stable dose of replacement therapy and abnormalities of thyroid hormones) of the prior therapy which have not been resolved to Grade 1 or less (based on CTCAE v.5.0)
• Subjects who have been discontinued from treatment due to drug-related toxicities with prior therapy directed against the same target as pembrolizumab
• Subjects who have received any anti-CTLA-4 monoclonal antibodies in the past
• Symptomatic central nervous system (CNS) metastases
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1) or any cancer curatively treated \> 3 years prior to study entry
• Any history of or current active cardiac disease/dysfunction including, but not limited to, any of the following:
• Cardiomyopathy
• Congestive heart failure \> NYHA class 2
• Coronary artery disease e.g. myocardial infarction, angina pectoris and symptomatic pericarditis
• Cardiac arrhythmias, e.g. supraventricular, ventricular or bradyarrhythmias
• lead electrocardiogram parameters at screening: QTc interval \> 450 msec, PR interval \> 220 msec, or QRS duration \> 109 msec
• Echocardiogram left ventricular ejection fraction \< 60% as determined by echocardiography at screening
• Abnormal MRI cardiac perfusion scan at screening

Sponsors & Collaborators

• New Beta Innovation Limited: lead

Study Sites (1)

The University of Hong Kong Phase I Clinical Trials Centre

Hong Kong, Hong Kong

Location

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Billy Lau, PhD.

  New Beta Innovation Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 dose escalation study composed of 2 stages. Single agent in Stage 1 (as defined as arm 1) and combination therapy in Stage 2 (as defined in arm 2)

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 14, 2020
• Study Start: August 21, 2020
• Primary Completion: July 26, 2023
• Study Completion: July 26, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)