A Phase I Study of Evaluating the Safety and Efficacy of Intravenous IDOV-SAFETM in Patients With Advanced Solid Tumors
Overview
- Phase
- Early Phase 1
- Intervention
- Oncolytic Virus injection(IDOV-SAFETM)
- Conditions
- Neoplasms
- Sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Incidence of adverse events and severe adverse events
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is an open-label, dose escalation, phase I study to evaluate safety tolerability, MTD or MFD, pharmacokinetic profile, immunogenicity, and pharmacodynamic profile of IDOV-SAFETM in patients with advanced solid tumors.
Detailed Description
The study is a single agent dose escalation which will use an accelerated and "3+3" design to evaluate escalating doses of IDOV-SAFETM.Total enrollment will depend on the toxicities and/or activity observed, with approximately 13-19 evaluable participants enrolled. A Dose-Limiting Toxicity (DLT) observation period of 3weeks was established before the entry of the first patient at the next dose level. After all subjects in the current dose group have completed the DLT observation period, the administration of the next dose group can only be started if the condition of dose escalation is met.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Understand and voluntarily sign a written informed consent;
- •Male and female, ≥18 years old and ≤75 years old;
- •Histologically or cytologically confirmed advanced malignant solid tumors that do not respond to standard treatment (disease progression or treatment intolerance after treatment) or currently lack effective standard treatment (including but not limited to advanced MSS colorectal cancer);
- •ECOG physical status score 0\~1;
- •Expected survival ≥3 months;
- •At least one evaluable lesion according to the solid tumor response criteria (RECIST version 1.1). Note: If the only evaluable disease site has previously received radiation therapy, it can be considered an evaluable lesion after determining disease progression;
- •Major organ and bone marrow functions meet the following criteria within 7 days prior to initial dosing:
- •Blood routine: neutrophils ≥1.5×109/L, platelets \> 100×109/L, hemoglobin ≥90g/L(no blood transfusion, no supportive treatment with G-CSF and other drugs within 2 weeks before screening);
- •Liver function: General patients: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)≤3× upper limit of normal; Total bilirubin ≤1.5× upper limit of normal value; Patients with liver metastasis: ALT and/or AST ≤5× upper limit of normal;
- •Renal function: serum creatinine (Cr)≤1.5× upper limit of normal value or creatinine clearance CCr≥60ml/min(using Cockcroft-Gault formula: The Ccr (ml/min) = \[(140 - age) \* weight kg \* F\] / \[serum creatinine (mg/dl) x 72\] (F = 1 male, the female F = 0.85).
Exclusion Criteria
- •Severe systemic reactions or side effects due to prior smallpox vaccination;
- •Patients with known to be allergic to the test drug or its excipients;
- •Patients with a history of other tumors within 5 years prior to screening, excluding effectively resected cervical carcinoma in situ, low-risk gastrointestinal stromal tumor, breast cancer, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and papillary thyroid carcinoma;
- •Patients with untreated symptomatic central nervous system metastases (CNS) who meet one of the following criteria can be enrolled:
- •CNS metastasis is asymptomatic and does not require treatment;
- •The CNS metastases have been treated, neurological symptoms have returned to baseline (except for treatment-related residual signs or symptoms), glucocorticoids have been discontinued for at least 2 weeks prior to randomization, and imaging studies within 28 days prior to randomization suggest that the CNS lesions are radiographically stable.
- •Pial metastasis;
- •Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Previous acceptance of oncolytic viruses, stem cells or gene therapy products;
- •Patients with received systemic antitumor therapy, including but not limited to chemotherapy, endocrine therapy, and immunotherapy, within 4 weeks before the first dose; Oral small-molecule targeted drugs are administered 2 weeks before the first dose or within 5 half-lives of the drug (whichever is longer); Palliative radiotherapy within 14 days before the first dose; Participated in clinical trials of other antitumor drugs within 4 weeks; Received any Chinese herbal medicine or proprietary Chinese medicine for any anti-tumor indication within 2 weeks prior to initial administration;
Arms & Interventions
Oncolytic Virus injection(IDOV-SAFETM)
Intravenous administration of IDOV-SAFETM as single agent for patients with advanced solid tumors. Dose cohorts: 1x10\^9 pfu、3x10\^9 pfu、1x10\^10 pfu and 3x10\^10 pfu
Intervention: Oncolytic Virus injection(IDOV-SAFETM)
Outcomes
Primary Outcomes
Incidence of adverse events and severe adverse events
Time Frame: Within day 85 after administration
Graded according to the NCI CTCAE version 5.0
Dose Limiting Toxicities (DLT)
Time Frame: Within day 21 after administration
Dose-limiting toxicity is defined as an adverse event that is considered to be drug-related and meets one of the Protocol definitions
MTD/MFD
Time Frame: Within day 21 after administration
To explore the maximum tolerated dose (MTD) or maximum administration dose (MFD) of IDOV-SAFETM in patients with advanced solid tumors.
Secondary Outcomes
- Immunogenicity of IDOV-SAFETM(Up to 85 days)
- DCR(Every 6 weeks (±7 days) after initial administration and every 12 weeks (±7 days) after 1 year)
- PFS(Every 6 weeks (±7 days) after initial administration and every 12 weeks (±7 days) after 1 year)
- The Pharmacokinetics characteristics of IDOV-SAFETM((biological distribution and viral expulsion))(Up to 2 days)
- ORR(Every 6 weeks (±7 days) after initial administration and every 12 weeks (±7 days) after 1 year)
- DOR(Every 6 weeks (±7 days) after initial administration and every 12 weeks (±7 days) after 1 year)
- OS(Up to death)