A Phase I Study Evaluating the Safety, Tolerability, Biodistribution and Shedding of the Virus, Pharmacodynamics, Immunogenicity, and Antitumor Activity of GC001 Oncolytic Vaccinia Virus Injection in Patient With Advanced Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patients With Advanced Solid Tumors
- Conditions
- Sarcoma
- Sponsor
- GONGCHU Biotechnology Co., Ltd
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Evaluate the safety and tolerability of GC001
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
The present trial is an open, single-arm phase I clinical study aimed at assessing the safety, tolerability, viral distribution and shedding patterns, pharmacodynamics, immunogenicity, and antitumor efficacy of GC001 oncolytic virus injection in patients with advanced solid tumors following a single administration.
Detailed Description
The main objective of this study is: To evaluate the safety and tolerability i.e. dose limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MFD) of GC001 injection in patients with advanced solid tumors. The ongoing trial is structured as an open, single-arm Phase I clinical study. The initial phase of the study, Part I, utilizes a 3+3 design to meticulously evaluate the escalation of the dose of GC001. The total enrollment of participants will be determined by the observed toxicity levels and the extent of dose cohorts explored, with an anticipated enrollment ranging from 21 to 36 eligible individuals. A critical 28-day period post-administration has been established for the observation of dose-limiting toxicities (DLTs) to ensure participant safety. It is essential to maintain this standardized 28-day observation window for all enrolled groups to uphold the highest safety standards. The secondary aims of this investigation are to assess the biodistribution and shedding of the virus, the pharmacodynamic characteristics, immunogenicity, and the initial antitumor efficacy of the GC001 injection in patients suffering from advanced solid tumors. These objectives are integral to understanding the broader impact and potential of the treatment in this patient population. Following the completion of the DLT assessment for all participants within each dose cohort, the SMC may decide whether to proceed with dose escalation, explore intermediate/higher doses, or terminate the dose escalation study based on the data obtained on safety, tolerability, biodistribution, and shedding of the virus (if any), pharmacodynamics (if any), immunogenicity (if any), and antitumor activity (if any). The SMC may also decide to adjust doses, administration schedules, and the time of biospecimen collection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for participation in this study, individuals must meet the following criteria:
- •Fully comprehend the purpose, nature, methods, and potential adverse effects of the trial, volunteer as a participant, and provide informed consent by signing the form prior to undergoing any procedures.
- •Be male or female patients aged 18 to 75 years (including those with borderline age values).
- •Patients with advanced solid tumors, including but not limited to: colorectal cancer, lung cancer, ovarian cancer, cervical cancer, etc., that have been histologically or cytologically diagnosed and for which there is either no current standard of care or the standard treatment has proven ineffective (progression of the disease after treatment or intolerance of treatment).
- •Possess at least one extracranial measurable lesion (as determined by a CT scan or MRI conducted no more than 4 weeks before signing the informed consent form) that is suitable for intratumoral injection based on RECIST v1.1 criteria.
- •Have an Eastern Cooperative Oncology Group (ECOG) physical status score of 0 or
- •Be expected to survive for at least 3 months.
- •Within 7 days prior to receiving the first dose of treatment, patients must meet the following organ function and bone marrow reserve:
- •Hematology: platelets (PLT) ≥ 80 × 109/L, neutrophil count (ANC) ≥ 1.5 × 109/L, and hemoglobin ≥ 9 g/dL (without having received adjuvants like EPO, G-CSF, or GM-CSF in the 14 days leading up to the first dose, and not having received a blood transfusion for at least 7 days);
- •Coagulation function: INR ≤ 1.2, APTT ≤ 1.2 × ULN (upper limit of normal), PT ≤ 1.2 × ULN;
Exclusion Criteria
- •Patients with a previous diagnosis of any other malignancy within 5 years prior to the first dose, except for malignancies with a low risk of metastasis and risk of death (5-year survival \> 90%), such as adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, and other carcinomas in situ.
- •Females of childbearing age who have a positive pregnancy test or are lactating.
- •Individuals with allergies (defined as ≥2 drug allergies) or hypersensitivity to similar products or excipients.
- •Those who have received smallpox vaccination and experienced severe systemic reactions or side effects.
- •Patients who have previously received lysosomal virus, stem cell, or gene therapy products.
- •Individuals using other investigational drugs or participating in clinical trials of other drugs within 28 days prior to the first dose (except for those who did not receive the test drug).
- •Those who have undergone antitumor therapy, including radiation therapy (except palliative radiotherapy), chemotherapy, biotherapy, endocrine therapy, and immunotherapy within 28 days prior to the first administration of the drug; Individuals using small molecule targeted agents with antitumor effects within 14 days prior to the first administration of the drug or within 5 times the half-life of the drug (whichever is longer); Individuals using herbal medicines with antitumor effects within 14 days prior to the first administration of the drug.
- •Individuals who have undergone surgery or interventional therapy (excluding tumor biopsy, puncture, etc.), or have unhealed wounds, ulcers, or fractures within 28 days prior to the first dose.
- •Individuals who have been treated with systemic corticosteroids (at a dose equivalent to \>10 mg prednisone/day) or other immunosuppressive medications within 28 days prior to the first dose, or who are currently taking antiviral medications (such as ribavirin, rifampin, imatinib, etc.), enrollment is permitted under the following cases:
- •short-term (≤7 days) use of corticosteroids for prophylaxis or treatment of non-autoimmune allergic diseases is permitted;
Arms & Interventions
Part 1: Dose Escalation
The study consists of a total of six dose groups, with the lowest dose group being 3×10\^6 and the highest dose reaching 1×10\^9 PFU. In case the maximum dose of 1×10\^9 PFU fails to achieve the Maximum Tolerated Dose (MTD), the Safety Monitoring Committee (SMC) will convene to discuss whether to designate it as Maximum Feasible Dose (MFD) or consider escalating further based on current safety and preliminary efficacy data. However, any escalation beyond that of similar drugs' Phase I clinical trials, such as JX-594:NCT00629759 and JX-929:NCT00574977, where the highest administered dose was 3×10\^9 PFU, shall be avoided. This precaution ensures adherence to established safety protocols. A single dose of GC001 will be administered up to 4mL (The injection volume is based on the length of the lesion).
Intervention: A Phase I Clinical Study of Intratumoral Injection Oncolytic Vaccinia Virus GC001 in Patients With Advanced Solid Tumors
Outcomes
Primary Outcomes
Evaluate the safety and tolerability of GC001
Time Frame: DLT Observation Period，Up to 28 days from GC001 injection
Number of participants in dose escalating cohorts with dose limiting toxicities (DLTs)，treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Maximal tolerable dose
Time Frame: DLT Observation Period,Up to 28 days from GC001 injection
During the DLT observation period, the number of cases with DLT is less than or equal to the maximum dose of 1/6 of the total number of cases, and six evaluable participants are required to determine MTD.
Secondary Outcomes
- Anti-tumor activity of GC001: duration of response (DOR).(Up to 2 years from GC001 injection)
- Anti-tumor activity of GC001: overall response rate (ORR).(Up to 2 years)
- Anti-tumor activity of GC001:progression-free survival (PFS).(Up to 2 years from GC001 injection)
- Evaluate the viral biological distribution and shedding of GC001(Up to 2 years from GC001 injection)