Intratumoral injection of BS006 for advanced solid tumors

A Phase 1, Open-label Study of BS006, an Oncolytic Virus, Administered by Intratumoral Injection in Patients with Advanced/Metastatic Solid Tumors

This study is testing a new injection called BS006 to see if it can safely help people with advanced solid tumors like melanoma and skin cancer that haven't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Binhui Biopharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 2 sites (Orlando, Florida and 1 other locations)
• Trial ID: NCT05938296 on ClinicalTrials.gov

What this trial studies

This Phase 1 clinical trial aims to evaluate the safety, tolerability, biodistribution, virus shedding, and preliminary efficacy of BS006, an intratumoral injection, in patients with advanced solid tumors. The study will involve a multi-center, open-label, dose escalation approach followed by an expansion phase at the recommended dose. Eligible patients include those with measurable solid tumors that have persisted or recurred despite previous therapies, specifically targeting advanced melanoma and cutaneous squamous cell carcinoma. The treatment period will consist of an initial three doses of BS006, with the possibility of extended treatment every two weeks for up to 12 months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced solid tumors that are measurable and have not responded to all available standard-of-care therapies.

Not a fit: Patients with solid tumors that are not measurable or those who have not exhausted standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have not responded to standard therapies.

How similar studies have performed: While this approach is novel, similar studies targeting advanced solid tumors with intratumoral therapies have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years old.
2. Subject must have histologically-only or histologically and cytologically confirmed diagnosis of solid tumors with palpable, visible or ultrasound detectable lesions (e.g., malignant melanoma, cutaneous squamous cell carcinoma and carcinoma of the breast).

   Subjects with tumors that are only confirmed by cytology are not eligible for this trial. Part 2 will only enroll subjects with advanced melanoma or CSCC.
3. Subject must have received and failed all available standard-of-care (SOC) therapies.

   Subjects who are intolerant to treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment will also be eligible for this study.
4. Subject has measurable disease as determined by RECIST version 1.1. At least 1 lesion must be suitable for intratumoral injection. Lesions for injection must be ≥ 10 mm and ≤ 60 mm in longest diameter.
5. Melanoma patients who were previously treated with IMLYGIC (Talimogene laherparepvec, T-Vec) are eligible after discontinuing the last dose of previous T-Vec treatment for ≥ 12 weeks before first dose of IP.
6. Subjects who have progressed on or are ineligible for available standard therapy are eligible for this trial after the last dose of the previous treatment which is ≥ 4 weeks or 5 half-lives(if required), whichever is longer before the first dose of study treatment.
7. Subject has a predicted life expectancy of ≥ 12 weeks.
8. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study treatment.Female subject must agree not to breastfeed from screening, throughout the study period and 180 days after the final study drug administration.
10. Females of childbearing potential must have a negative urine or serum pregnancy test within one week prior to start of treatment.
11. Subject must be willing and able to comply with the study requirements including prohibited concomitant medication restrictions.
12. Subject agrees not to participate in another interventional study while receiving study drug.
13. Subject has the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Subject has ongoing toxicity ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2 attributable to prior antineoplastic therapies considered clinically significant.
2. Subject has had major surgery ≤ 4 weeks of screening.
3. Subject is concurrently participating in another interventional study or has received an investigational product ≤ 30 days or 5 half-lives prior to first study drug administration.
4. Subject with symptomatic central nervous system (CNS) metastases, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months and have been off steroids for at least 4 weeks prior to first IP administration.
5. Subject with active autoimmune disease requiring systemic therapy within past 2 years (e.g., systemic lupus erythematosus, Wegener syndrome (granulomatosis with polyangiitis),

   Graves' disease, hypophysitis, etc,). The following are exceptions to this criterion:
   * Subject with vitiligo or alopecia
   * Subject with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
   * Childhood asthma that has resolved
   * Any chronic skin condition that does not require systemic therapy
   * Type 1 diabetes mellitus ※Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
6. Subject with another malignancy that currently requires treatment.
7. Subject with tumors encasing major vascular structures such as the carotid artery, tumors adjacent to vital neurovascular structures or tumors in locations that are at high risk for AEs or otherwise not considered appropriate for IT injection.
8. Subject with inadequate organ and marrow functions meeting any of the below criteria:

   * Leukocytes \< 3000/μL
   * Absolute neutrophil count \< 1500/μL (Subjects treated with G-CSF or GM-CSF within 14 days prior to screening will not be enrolled.)
   * Platelets \< 100,000/μL (Subjects with a platelet transfusion, or treated with TPO, TPO receptor agonist or IL11 within 14 days prior to screening will not be enrolled.)
   * Hemoglobin (Hgb) \< 9 g/dL (Subjects with a blood transfusion or treated with EPO within 14 days prior to screening will not be enrolled.)
   * International normalized ratio (INR) \> 1.5 × ULN and/or activated partial thromboplastin time (aPTT) \> 1.5 × institutional normal limits
   * Total Bilirubin (TBL) \> 1.5 × institutional normal limits (subjects with known Gilbert syndrome who are excluded if TBL \> 3.0 × institutional normal limits or direct bilirubin \> 1.5 × institutional normal limits)
   * Aspartate aminotransferase (AST) and Alanine transaminase (ALT) \> 3.0 × institutional normal limits. Subjects with tumors in the liver AST and ALT \> 5 × institutional normal limits.
   * Albumin \<3.0 g/dL
   * Estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73 m2 (It is calculated according to the CKD-EPI formula)
9. Subject with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of study drug. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
10. Subject has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (e.g., subjects with active herpetic skin lesions or prior complications of herpetic infection (e.g., herpetic keratitis or encephalitis), or subjects requiring intermittent or chronic systemic (intravenous or oral) treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use), symptomatic congestive heart failure, any form of substance abuse or psychiatric illness/social situations that would limit compliance with study visits or requirements, or a condition that could invalidate communication with the Investigator.
11. Subject is known to be positive for human immunodeficiency virus, hepatitis B surface antigen, hepatitis B core immunoglobulin or immunoglobulin G (IgG) antibody, or hepatitis C (IgG or ribonucleic acid (RNA) test) indicating acute or chronic infection.
12. Subject has a history of moderate to severe ascites, clinically significant and/or rapidly accumulating ascites, bleeding esophageal varices, hepatic encephalopathy, or pericardial and/or pleural effusions related to liver insufficiency within 6 months of screening. Mild ascites that does not preclude safe IT injection of BS006 is allowed.
13. Subject has a clinically significant abnormal electrocardiogram (ECG) at screening.
14. Subject has symptomatic cardiovascular disease within the preceding 12 months unless cardiology consultation and clearance has been obtained for study participation, including but not limited to the following: significant coronary artery disease (e.g., requiring angioplasty or stenting), acute myocardial infarction or unstable angina pectoris \< 3 months prior to screening, uncontrolled hypertension, clinically significant arrhythmia, or congestive heart failure (New York Heart Association grade ≥ 2).
15. Subject who has a history of bleeding diathesis, are on anti-coagulation therapy, or have abnormal coagulation-fibrinolytic parameters (e.g., activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and platelet count).
16. Subject has medical conditions that predispose the subject to untoward medical risk in the event of volume loading (e.g., intravenous fluid bolus infusion), tachycardia, or hypotension during or following treatment with BS006.
17. Subject has a known or suspected hypersensitivity to BS006 or any components of the formulation used, including prior adverse reaction to vaccinia (e.g., as smallpox vaccine).
18. Subject has had previous exposure with BS006

Where this trial is running

Orlando, Florida and 1 other locations

• Orlando Health Cancer Institute — Orlando, Florida, United States (Recruiting)
• Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center — Detroit, Michigan, United States (Recruiting)

Study contacts

• Study coordinator: Yue Su

Conditions Solid Tumor