Dose Escalation and Cohort Expansion Study of YS-ON-001 in Patients With Advanced Solid Tumors

NCT03131765 | Completed Phase 1 DMC

• 1 other identifier: YS-RVON-001
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 study evaluating the safety and tolerability of YS-ON-001 in patients with advanced solid tumors who have limited available treatment options, and exploratory evaluation of the pharmacological effect and efficacy of YS-ON-001. The study will be conducted in two parts: dose escalation and cohort expansion

Conditions

Cancer

Outcome Measures

Primary Outcomes (3)

• Safety of YS-ON-001 by monitoring any adverse events (AE) and serious adverse events (SAE)

  To assess the safety of YS-ON-001 in patients with advanced (metastatic and/or unresectable) solid tumors based on the identification of any adverse events through study completion

  through study completion, an average of 1 year

• Tolerability of YS-ON-001 by recording AE /SAE, clinically significant changes in lab parameters and performance status (ECOG)

  To assess the tolerability of YS-ON-001 in patients with advanced (metastatic and/or unresectable) solid tumors for recommended phase II dose (RP2D)

  6 months

• Dose-limiting toxicities (DLT)

  Number of Participants with a Dose Limiting Toxicity (DLT)

  For 4 weeks for DLTs

Secondary Outcomes (2)

• Antitumor Activity of YS-ON-001 by imaging measurement and assessing using RECIST Version 1.1

  At 2 months, 4 months., 6months, 9 months and 1 year

• Immunogenicity of YS-ON-001 evaluated by measuring serum titre level antibody against YS-ON-001

  At 3 months, 6 months, 9 months and 1 year

Study Arms (1)

YS-ON-001

EXPERIMENTAL

Phase 1- Dose escalation based on YS-ON-001 safety and tolerability obtained from three subjects enrolled in a cohort (first cycle of treatment), enrollment at the next dose level or additional subjects into the ongoing cohort will occur. Phase 1b- recommended dose determined in Phase 1. Enrollment of two expansion cohorts will be restricted to the tumour types, breast cancer and liver cancer

Biological: YS-0N-001

Interventions

YS-0N-001 BIOLOGICAL

Cancer vaccine

Also known as: Polyinosinic-polycytidylic acid/inactivated rabies virus

YS-ON-001

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Life expectancy ≥ 3 months
• Patient with histologically or cytologically proven advanced (unresectable) or metastatic solid tumor who have failed standard therapies or are intolerant to standard therapies.Part 1: Any advanced or metastatic solid tumor patient Part 2: Selected tumor types including cytological or histologically diagnosed breast cancer and liver cancer
• Patients with adequate bone marrow function, with absolute neutrophil count (ANC) \>1,500/mm3, platelet count \>100,000/mm3, and hemoglobin \> 10 g/mm3
• Patients with adequate kidney function, with serum creatinine ≤1.5 X upper limit of normal (ULN)
• Patients with adequate liver function, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN, total bilirubin ≤1.5x ULN ; For patients with liver metastasis, AST, ALT ≤5x ULN, Total bilirubin ≤1.5x ULN
• Patients with adequate coagulation function, with activated partial thromboplastin time (aPTT) ≤1.5x ULN
• Female patients, if of childbearing potential, must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication.
• Female patients of childbearing potential and male patients must agree to use adequate methods of contraception with their partner starting with the screening visit up to 4 weeks after the last dose of study therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

You may not qualify if:

• Known uncontrolled seizures, central nervous system disorders, or loss of cognitive ability due to mental illness
• Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study.
• Patient is currently receiving or has received systemic corticosteroids within 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. The following use of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airway diseases), eye drops or local injections (e.g., intra-articular).
• Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
• Known serious, uncontrolled medical conditions that in the opinion of the investigator, will render it unsafe for the patient to receive the study therapy
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Patient has not recovered (i.e., to ≤ Grade 1 or to baseline) from radiation- and chemotherapy-induced adverse events (AEs) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF) or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug.
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational drug within 4 weeks prior to the first dose of study drug.
• Received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter. Note: palliative radiation therapy to a small field ≥ 1 week prior to Day 1 of study treatment will be allowed.
• Patient has not recovered adequately (≤ Grade 1) from AEs and/or complications from any major surgery prior to starting therapy. Patient has received a vaccine within 7 days of planned start of study therapy.
• Known hypersensitivity to YS-ON-001 components or excipients
• Known unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction that occurred within a year, severe arrhythmia that required drug treatment, liver disease, kidney disease and metabolic diseases)
• Known history of splenectomy
• Known history of chronic alcohol or drug abuse within 6 months
• PI assessment of subject's lack of willingness to participate and comply with all requirements of the protocol

Sponsors & Collaborators

• Yisheng Biopharma (Singapore) Pte. Ltd.: lead

Study Sites (1)

National University Cancer Institute Singapore

Singapore, Singapore

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Lee Soo Chin

  National University of Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: YS-ON-001 is a single agent used for this study

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: April 27, 2017
• Study Start: April 20, 2017
• Primary Completion: December 15, 2019
• Study Completion: December 16, 2019
• Last Updated: December 5, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)