Trial Title:
oHSV2-PD-L1/CD3-BsAb Administered Via Intratumoral Injection
NCT ID:
NCT05938296
Condition:
Solid Tumor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BS006 Injection
Description:
BS006 will be given every two weeks, and up to 4mL in each treatment. There will be three
dose levels: 1×10^6 CCID50/mL, 5×10^6 CCID50/mL, 1×10^7 CCID50/mL.
Arm group label:
BS006 injection
Other name:
oHSV2-PD-L1/CD3-BsAb
Summary:
This study will be a Phase 1, multi-center, open-label, dose escalation followed by the
recommended phase 2 dose (RP2D) expansion study to characterize safety, tolerability,
biodistribution, virus shedding and preliminary efficacy of intratumoral injection of
BS006 in patients with advanced solid tumors.
Detailed description:
Eligible patients are those who have measurable solid tumors as detected by CT or MRI
that have persisted, recurred, or metastasized despite therapy. Patients must have
histologically confirmed advanced and/or metastatic melanoma, cutaneous squamous cell
carcinoma and other solid tumors with palpable, visible or ultrasound detectable lesions.
Also, patients with solid tumors that are refractory to standard therapy and for which no
existing conventional therapy are eligible. Melanoma patients who were previously treated
with IMLYGIC (Talimogene laherparepvec, T-Vec) but did not achieve an optimal response to
T-Vec are eligible to receive BS006.
The study will be conducted in 2 parts as described below. Both parts will consist of a
screening period of up to 28 days, a treatment period and a follow-up period (safety and
long-term follow up). Treatment period of Part 1 will include an initial treatment period
(3 doses of BS006) and an optional extended treatment period (repeated every 2 weeks).
Subjects will be treated for up to 12 months.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Orlando Health Cancer Institute
Address:
City:
Orlando
Zip:
32806
Country:
United States
Status:
Recruiting
Contact:
Last name:
Weiyu Yang
Facility:
Name:
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Weiyu Yang
Start date:
December 19, 2023
Completion date:
January 1, 2026
Lead sponsor:
Agency:
Binhui Biopharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Binhui Biopharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05938296
