Dose Escalation/Dose Expansion Study of YBL-006 in Patients With Advanced Solid Tumors

NCT04450901 | Unknown Phase 1 DMC

• 1 other identifier: YBL006C101
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 7

Brief Summary

This is a Phase 1/2a, open-label, multicenter, dose-escalation/dose-expansion study of YBL-006, in participants with Advanced Solid Tumors. This multicenter study will be conducted in approximately 11-14 participants in the dose escalation phase, and approximately 39-76 participants in dose expansion phase.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Safety and tolerability measure through Adverse Events/Serious Adverse Events

  Treatment-related adverse events as assessed by CTCAE v5.0 or higher

  Measurements at Baseline till Follow up from 90 days of last dose

• Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign- blood pressure

  Measured by result of the Vital Sign- blood pressure

  Measurements at Baseline till Follow up from 90 days of last dose

• Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Vital Sign-heart rate

  Measured by result of the Vital Sign- heart rate

  Measurements at Baseline till Follow up from 90 days of last dose

• Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through 12-lead ECG

  Measured by result of the ECG QT Interval

  Measurements at Baseline till Follow up from 90 days of last dose

• Safety and tolerability(Incidence of Treatment-Emergent Adverse Events) measure through Physical exam

  Measured by result of the physical exam which includes general appearance, skin, eyes/ears/nose/throat, head and neck.

  Measurements at Baseline till Follow up from 90 days of last dose

• To establish the recommended Phase 2 dose (RP2D) of YBL-006 in patients with advanced solid tumors

  Measured through increase in anti-drug antibody (ADA) levels

  Measurements at Baseline

Secondary Outcomes (3)

• pharmacokinetic (PK) profile of YBL-006

  Measured at C1D1 till Follow up from 90 days of last dose

• pharmacokinetic (PK) profile of YBL-006

  Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose

• pharmacokinetic (PK) profile of YBL-006

  Measured at Cycle1(each cycle is 28 days) Day1 till Follow up from 90 days of last dose

Study Arms (8)

Cohort A1 group

EXPERIMENTAL

YBL-006 will be administered once every 2 weeks (Q2W). Dose: 0.5 mg/kg

Drug: YBL-006

Cohort A2 group

EXPERIMENTAL

YBL-006 will be administered once every 2 weeks (Q2W). Dose: 2 mg/kg

Drug: YBL-006

Cohort A3 group

EXPERIMENTAL

YBL-006 will be administered once every 2 weeks (Q2W). Dose: 5 mg/kg

Drug: YBL-006

Cohort A4 group

EXPERIMENTAL

YBL-006 will be administered once every 2 weeks (Q2W). Dose: 10 mg/kg

Drug: YBL-006

Cohort B1

EXPERIMENTAL

Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments). YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg

Drug: YBL-006

Cohort B2

EXPERIMENTAL

Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments). YBL-006 will be administered once every 3 weeks (Q3W). Dose: 300 mg

Drug: YBL-006

Cohort B2 reserve

EXPERIMENTAL

Tumor type: Advanced Solid tumor (unresectable, locally advanced, or metastatic and have progressed following all standard treatments or are not suitable for standard treatments). YBL-006 will be administered once every 2 weeks (Q2W). Dose: 300 mg

Drug: YBL-006

Cohort B3

EXPERIMENTAL

Tumor type: Metastatic NSCLC (Non-small-cell lung carcinoma), unresectable or metastatic, MSI-H (microsatellite instability-high) or dMMR (Deficient MisMatch Repair), recurrent or metastatic HNSCC (Head and neck squamous cell carcinoma), non-clear cell RCC (renal cell carcinoma), aSCC (anal squamous cell carcinoma), uterine cervical cancer, cSCC (cutaneous squamous cell carcinoma of the skin), uterine endometrial carcinoma, TMB-H (high tumor mutation burden) tumors, epithelial tumor of the penis (squamous cell carcinoma or adenocarcinoma), neuroendocrine tumor (any origin, pancreatic or non-pancreatic), and nasopharyngeal cancer. YBL-006 will be administered once every 2 weeks (Q2W). Dose: 200 mg

Drug: YBL-006

Interventions

YBL-006 DRUG

Route of Administration: IV infusion; 0.5 mg/kg Q2W

Also known as: Cohort A1

Cohort A1 group

Eligibility Criteria

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

You may qualify if:

• Written consent on an IRB/ IEC-approved ICF prior to any study-specific evaluation.
• Male or female aged ≥18 years (or age of legal adult, whichever is older).
• Life expectancy of at least 3 months.
• ECOG performance status of 0 to 1.
• Availability of archival tumour tissue and consent to provide archival tumour for retrospective biomarker analysis, or consent to undergo a fresh tumour biopsy during screening. Participants who do not have an existing (archived) tumour specimen and are unwilling to undergo a biopsy may be enrolled with prior approval from the Sponsor.
• For participants in dose escalation only: Histologically confirmed solid tumours (except primary CNS tumours) that are unresectable, locally advanced, or metastatic and have progressed following all standard treatments or is not appropriate for standard treatments.
• Must have at least one measurable lesion based on RECIST Version 1.1. A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable and there is objective evidence of interval increase in size.
• CNS metastasis must be without evidence of progressive neurological symptoms or requires increasing doses of corticosteroids to control the CNS disease for at least 4 weeks. If a participant requires corticosteroids for management of CNS disease, the dose must have been stable with low-dose (same or less than 10 mg/day prednisone or equivalent) for at least two weeks preceding C1D1.
• Immunosuppressive doses of systemic medications, such as steroids (doses \> 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before IP administration.
• Prior surgery that required general anaesthesia must be completed at least 14 days before IP administration. Surgery requiring local/epidural anaesthesia must be completed at least 72 hours before IP administration and participants should be recovered.
• Adequate haematological and biological function, confirmed by the following laboratory values:
• Neutrophils ≥ 1000/μL Platelets ≥ 75,000/μL Haemoglobin ≥ 9.0 g/dL (may have been transfused) Creatinine ≤ 1.5×upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 2.5×ULN (Except with liver metastasis, AST ≤ 5×ULN) Alanine aminotransferase (ALT) ≤ 2.5×ULN (Except with liver metastasis, AST ≤ 5×ULN) Bilirubin ≤ 1.5×ULN (except participants with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL).
• Women must meet 1 of the following criteria: postmenopausal for at least 24 consecutive months; surgically incapable of bearing children (i.e., have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception. In general, the decision for appropriate methods to prevent pregnancy should be determined via discussions between the Investigator and the study participant. WOCBP must agree to use a reliable form of contraceptive during the study Treatment Period and for at least 120 days following the last dose of IP.
• Men must agree to the use of acceptable contraceptive use and avoid sperm donation, during the study Treatment Period and for at least 180 days after the last dose of IP.
• Confirmed diagnosis of one of the following tumour types:

You may not qualify if:

• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Chemotherapy, radiation therapy, biological cancer therapy, or tyrosine kinase inhibitor (TKI) therapy within 2 weeks or 5 half-lives (whichever is the longer)prior to the first dose of IP, or who has not recovered to National Cancer Institute (NCI)- Common Terminology Criteria for Adverse Events (CTCAE) version 5 or higher Grade 1 or better from the AEs due to cancer therapeutics administered more than 2 weeks earlier; (palliative radiation treatment with a limited field of radiation is allowed up to 14 days prior to first dose of YBL-006).
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, or localized prostate cancer.
• Active infection (viral, bacterial, or fungal) requiring IV antimicrobial treatment within 14 days before the first dose of YBL-006.
• Has known chronic Hepatitis B (e.g., HBsAg reactive) without sufficient anti-viral treatment (prior treatment duration should be more than 3 months), Hepatitis C infection, or human immunodeficiency virus (HIV).
• Has active or history of interstitial l.ng disease (ILD), or has had a history of pneumonitis that has required oral or IV steroids.
• Evidence of bleeding diathesis.
• Any active or suspected autoimmune disease or a documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy.
• Receipt of live, attenuated vaccine within 28 days prior to the first dose of IP (Note: Participants, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of IP). Vaccination with a killed vaccine is permitted at any time with consultation with the Medical Monitor. Patients may receive vaccination for SARS-CoV-2 (DNA or mRNA vaccine) at the discretion of the Investigator as soon as they are eligible, and a vaccine is available.
• Known current drug or alcohol abuse.
• Apparent active or latent tuberculosis infection (purified protein derivative \[PPD\] test is not required) as indicated by any of the following: PPD recently converted to positive; chest x-ray with definitive evidence of active infectious infiltrate.
• Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the Investigator, would make the participant inappropriate for entry into the study.
• Concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic corticosteroids (doses 10 mg/day prednisone or equivalent). Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the participant is on a stable dose. Non-absorbed intra-articular steroid injections will be permitted.
• Use of other investigational therapy within 28 days before IP administration.

Sponsors & Collaborators

• Y Biologics Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (7)

Macquarie University

Macquarie, New South Wales, 2109, Australia

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Study Officials

• Yoon Jaebong

  Y-Biologics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 30, 2020
• Study Start: July 1, 2020
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: December 5, 2022

Record last verified: 2022-12

Locations

TH (1); AU (1); KR (5)