Cervical Cancer, HNSCC, HPV 16+ Recurrent or Metastatic Cancer
Conditions
Keywords
Therapeutic tumor vaccine, Circular RNA
Brief summary
This is a phase I, open-label, dose escalation study to assess the safety, tolerability, efficacy and immunogenicity of TI-0093 injection in patients with recurrent or metastatic HPV-16 positive solid tumors. The primary objectives of the study are to assess safety and tolerability of TI-0093 injection in patients with recurrent or metastatic solid tumors, and to determine the maximum tolerated doses (MTDs) and recommended Phase 2 doses (RP2Ds) of TI-0093 injection.
Detailed description
All potential study candidates will provide informed consent and undergo screening procedures to determine their study eligibility. After a screening period of up to 28 days, qualified patients will be enrolled to receive their assigned dose of TI-0093 injection. Patients will receive a total of five doses of TI-0093 administered muscularly on Day1, Day8, Day15, Day29 and Day43, respectively. Dose-limiting toxicities (DLTs) will be assessed for at least 28 days after the first dose of a given regimen. During the study, patients will be evaluated for safety, toxicity, immunogenicity, ORR, DOR, DCR, and PFS per protocol.
Interventions
BIOLOGICALtherapeutic tumor vaccine
TI-0093 injection will be administered intramuscularly on Day1, Day8, Day15, Day29 and Day43.
Sponsors
Therorna
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all the following inclusion criteria to be eligible for participation in this study: 1. The patient provides written informed consent for the study. 2. Willing to comply with the visit plans, treatment plans, and other requirements of the study schedule. 3. Previous HPV16+ solid tumors. 4. 18 to 75 years of age at the time of informed consent. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration over the previous 2 weeks. 6. Estimated life expectancy of more than 12 weeks. 7. Previous HPV16 positive head and neck, cervical and other carcinoma patients with recurrent or metastatic disease, who have progressed after standard therapies, or for whom no further standard therapies are available. 8. Patients should have at least 1 measurable lesion at baseline according to the definition of RECISTv1.1. 9. Absolute neutrophil count ≥ 1.5 ×10\^9/L, without the use of granulocyte colony stimulating factors such as filgrastim within 2 weeks prior to study treatment. Platelet count ≥ 100 × 10\^9/L without transfusion within 2 weeks (≤ 14 days) prior to study treatment. Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment. 10. Aspartate transaminase and alanine aminotransferase ≤ 3 × upper limit of normal (ULN) (patients with liver metastasis \< 5 × ULN), and total bilirubin ≤ 1.5 × ULN (patients with Gilbert's Syndrome ≤ 3 × ULN). 11. Adequate renal function defined by either a creatinine clearance ≥ 45 mL/min (by Cockcroft-Gault formula) or serum creatinine \< 1.5 × ULN. 12. Prothrombin time ≤ 1.5 × ULN; activated partial thromboplastin time ≤ 1.5 × ULN; international normalized ratio ≤ 1.5 × ULN. 13. Left ventricular ejection fraction ≥ 50% measured by echocardiogram. 14. Females of childbearing potential and males whose partners are of childbearing potential agree to the use effective contraception from signing informed consent form to 90 days after the last dose of TI-0093 injection. The test results of HCG of females with childbearing potential should be negative within 7 days prior to the first dose of TI-0093 injection.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | From enrollment to 28 days post the last dose of TI-0093 injection | The safety profiles of TI-0093 injection will be assessed in terms of severity, seriousness, frequency of AEs, laboratory results, vital signs, physical examinations, and 12-lead electrocardiogram of the patients enrolled in the study. |
| DLTs | From enrollment to 3 months. | DLTs will be assessed for at least 28 days after the first dose TI-0093 injection of a given regimen. Toxicities will be assessed by the National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) v5.0. |
| RP2D | From enrollment to 3 months. | The RP2D will be determined based on the observation of MTD. |
Countries
China
Contacts
Primary ContactYe Guo
Backup ContactThe Drug Clinical Trial Institution of Shanghai East Hospital
Outcome results
None listed