A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Biologic Effect of VG2025 as a Single Agent and in Combination Therapy With Nivolumab in Subjects With Advanced Malignant Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- VG2025
- Conditions
- Solid Tumor
- Sponsor
- Virogin Biotech Canada Ltd
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Incidence of Adverse Events
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, open-label, dose-escalation trial using standard 3+3 dose-escalation design in patients with advanced malignant solid tumors. All patients within a given dose level cohort will be treated with the same dose schedule of VG2025, administered as intratumoral injections at Day 1 and Day 15 biweekly at each treatment cycle (monotherapy cohorts 1-4 and combination cohort 1) and on day 1 and either day 2 or day 3 at the first 2 cycles followed by day 1 only at subsequent cycles (combination cohort 2). Dose limiting toxicity (DLT) evaluation period is for 4 weeks, from the start of treatment, Day 1, through Day 28.
There are two parts to this study a monotherapy arm and a combination therapy arm. In the monotherapy arm the patients will receive VG2025 only. In the combination therapy arm the patients will receive VG2025 and Nivolumab
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent.
- •Males or females aged ≥ 18 years.
- •Performance status: Eastern Cooperative Oncology Group (ECOG) 0 or
- •Subject with advanced malignant solid tumors which is refractory/relapsed after and/or intolerant of standard therapies or for which no standard therapy exists or available (refer to National Comprehensive Cancer Network \[NCCN\] guideline).
- •At least 1 injectable cutaneous or subcutaneous lesion ≥15 mm in longest diameter and/or nodal lesions that are visible or palpable deemed injectable.
- •Seropositive for Herpes Simplex Virus (HSV).
- •Had an interval of ≥4 weeks (28 days) since exposure to immunotherapy, an interval of ≥3 weeks (21 days) since exposure to systemic chemotherapy, an interval of ≥6 weeks (42 days) since exposure to nitrosourea, and an interval of ≥4 weeks (28 days) since exposure to radiotherapy, prior to dosing.
- •Life expectancy of at least 3 months.
- •Eligibility requirements also include:
- •Hemoglobin ≥ 90 grams (g)/liter (L),
Exclusion Criteria
- •Participation in any previous immunotherapy trial or any trial of any other investigational agent if half-life is more than 5 days within the last 4 weeks prior to dosing.
- •Tumors to be injected lying in mucosal regions or close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigator could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis.
- •Subjects with any primary Central Nervous System (CNS) malignancy including glioma and current, active, progressing CNS malignancy, including carcinomatosis meningitis are excluded. Subjects with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan) during the screening period and off systemic steroids (for at least 2 weeks prior to first dose of VG2025).
- •Major surgery within 14 days prior to Screening commencement.
- •Intercurrent serious infections within 28 days prior to Screening or treated systematically with intravenous antibiotics within 14 days prior to Screening.
- •Life-threatening illness unrelated to cancer.
- •Active Herpes or COVID-19 infections
- •Treatment with antiviral agents within 14 days prior to Screening commencement.
- •Subjects with congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
- •Known to test positive for human immunodeficiency virus (HIV), hepatitis B or C virus, or syphilis.
Arms & Interventions
Monotherapy Arm
This is an open label trial using standard 3+3 design, in up to 24 HSV seropositive subjects. This rule-based design proceeds with cohorts of three patients.
Intervention: VG2025
Combination Arm
The starting dose of VG2025 in the combination cohorts will be a dose of 1.0 x108 PFU for combination cohort 1 on days 1 and 15 of every cycle. Combination cohort 2 will be dosed at 1.0 x108 PFU on Day 1 and either Day 2 or 3 in cycle 1 and 2. Day 1 only in subsequent cycles
Intervention: VG2025
Combination Arm
The starting dose of VG2025 in the combination cohorts will be a dose of 1.0 x108 PFU for combination cohort 1 on days 1 and 15 of every cycle. Combination cohort 2 will be dosed at 1.0 x108 PFU on Day 1 and either Day 2 or 3 in cycle 1 and 2. Day 1 only in subsequent cycles
Intervention: Nivolumab Injection [Opdivo]
Outcomes
Primary Outcomes
Incidence of Adverse Events
Time Frame: 12 months
Incidence of Adverse Events as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
MTD
Time Frame: 12 months
Recommended Phase 2 Dose
Secondary Outcomes
- Level of deoxyribonucleic acid (DNA)(12 months)
- interleukin level(12 months)
- ADA level of VG2025(12 months)
- Nab level of VG2025(12 months)
- ORR(12 months)
- DoR(12 months)
- DCR(12 months)
- PFS(12 months)