Advanced solid tumors
Conditions
Interventions
Phase I PART A :PTT-OV001 Injection Single Drug Dose Escalation
Phase I PART B:PTT-OV001 Injection Single Dose Extension
Phase II:PTT-OV001 Injection Combined with PD-1 Antibody Dose Escalation
Sponsors
Langfang Campus of Cancer Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntary signing of the informed consent form (ICF); 2. Ability and willingness to comply with all study procedures; 3. Age of the patient >= 18 years at the time of signing the ICF; 4. Presence of locally advanced unresectable or metastatic solid tumor confirmed by histological or cytological examination; 5. Must have a lesion that can be locally injected, including superficial tumor tissue or deep tumor tissue; 6. Expected survival time >= 3 months; 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1; 8. Adequate end-organ and hematopoietic function (defined by the following laboratory results obtained within 7 days before the first dose): (1). Absolute neutrophil count (ANC) >= 1.0×10^9/L without granulocyte colony-stimulating factor (G-CSF) support. Note: Short-acting G-CSF administration can continue until 7 days before C1D1, and long-acting G-CSF administration can continue until 14 days before C1D1; (2). Platelet count >= 80×10^9/L without blood transfusion within 14 days before C1D1; (3). Hemoglobin >= 90 g/dL (9 g/dL). Note: To meet this criterion, patients can receive blood transfusion or erythropoietin treatment within 14 days before C1D1; (4). Creatinine clearance >= 50 mL/min. (5). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 3× upper limit of normal (ULN). Note: For primary hepatocellular carcinoma/bile duct carcinoma, it should be <= 5×ULN. (6). Total bilirubin (TBIL) <= 1.5×ULN. Note: For primary hepatocellular carcinoma/bile duct carcinoma, it should be <= 2×ULN; (7). For patients not receiving anticoagulant therapy: international normalized ratio (INR), activated partial thromboplastin time (aPTT), and prothrombin time (PT) <= 1.5×ULN; (8). For patients receiving warfarin treatment: INR <= 3.0×ULN, and no bleeding within 14 days before the first dose. Patients receiving anticoagulant therapy must have received a stable dose for at least 14 days before the first dose. Patients receiving low-molecular-weight heparin are allowed to be enrolled. 9. For women of childbearing age (see Appendix I): Must agree to remain completely abstinent or use at least one acceptable contraceptive method from screening to 3 months after the last dose of study drug. Acceptable contraceptive methods refer to those with a low failure rate (i.e., <1% per year) when used alone or in combination, such as intrauterine devices, hormonal contraception, and barrier methods (e.g., condom with spermicidal foam/gel/film/pill). Female subjects must avoid donating eggs; 10. For men with sexual activity whose female partners are of childbearing age: Must agree to remain completely abstinent or use barrier methods (e.g., condom with spermicidal foam/gel/film/pill) from screening to 3 months after the last dose of study drug. Male subjects must not donate sperm during this period. Male patients who have undergone vasectomy for more than 6 months before the first dose are exempt from this criterion.
Exclusion criteria
Exclusion criteria: 1. Patients who have previously received systemic or local oncolytic virus therapy; 2. Patients who had leptomeningeal (LMD) metastasis or new and/or progressive brain metastases at the time of enrollment. If, during the screening period, no evidence of progression was found within at least 4 weeks after receiving central nervous system (CNS) targeted treatment (radiation and/or surgery) through clinical examination and brain imaging (MRI or CT), then patients with treated brain metastases are eligible to participate in this study; 3. Before the first administration, in addition to the study-related disease, there is a history of other primary malignant tumors, and the remission period has not exceeded 2 years. Exceptional cases that do not require a 2-year remission period include: adequately treated non-melanoma skin cancer, confirmed cervical carcinoma in situ or squamous intraepithelial lesion as shown by a Pap smear, prostatic carcinoma in situ (with no evidence of active disease within 2 years before the first administration), or resected in situ melanoma and surgically resected papillary thyroid carcinoma; 4. The adverse events (AEs) caused by previous cancer treatment persist and have not subsided to grade 1 (except for alopecia and hypothyroidism), or have any grade >= 3 CRS, grade >= 3 drug-related CNS toxicity history, any grade of immune therapy-related pituitary inflammation or encephalitis; 5. Active systemic autoimmune diseases or a history of autoimmune diseases that are likely to recur (such as systemic lupus erythematosus [SLE], rheumatoid arthritis, inflammatory bowel disease [IBD], autoimmune thyroid disease*, multiple sclerosis, vasculitis, glomerulonephritis, eczema, psoriasis, etc.). • *Note that patients with controlled primary or secondary hypothyroidism through hormone replacement therapy are allowed to enroll; 6. Within 4 weeks before the first administration, suffered from major trauma or undergone major surgery, or are expected to undergo major surgery during the participation in the study; 7. Have severe, non-healing wounds, ulcers or fractures. 8. Any of the following cardiovascular and cerebrovascular events or diseases occurred previously or currently exist: (1). Within 12 months prior to the first administration, there was a myocardial infarction, unstable or severe angina pectoris, or arterial thrombosis event (such as cerebrovascular attack [CVA] or transient ischemic attack [TIA]); (2). During the screening, significant abnormalities were detected in the ECG, including a QTc interval > 470 msec (average of three measurements, corrected by the Fridericia formula for heart rate), second-degree (Moy's type II) or third-degree atrioventricular (AV) conduction block, or other (as deemed clinically significant) arrhythmias; (3). Currently, there is New York Heart Association (NYHA) class II-IV congestive heart failure (CHF); (4). Left ventricular ejection fraction (LVEF) = 150 mmHg and/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Antitumor activity of single-agent treatment;safety and tolerability of combined treatment;anti-tumor activity of combined therapy;Pharmacokinetic characteristics and the situation of virus shedding;The changes in immune indicators related to pharmacodynamics;Biological markers related to therapeutic efficacy; | — |
Countries
China
Contacts
Public ContactNing Li
Langfang Campus of Cancer Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed