Advanced malignant solid tumors
Conditions
Interventions
Experimental group:PM8003
Control group:None
Sponsors
Shanghai Orient Hospital
Eligibility
Sex/Gender
Male
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Voluntary participation in clinical studies; Fully understand the study and sign the informed consent voluntarily; Willing to follow and able to complete all test procedures; 2.Male or female, 18 to 75 years old (including the boundary value); 3.Subjects with advanced malignant solid tumor confirmed by histology or cytology; (1) Single-drug study 1)Phase I dose escalation and preliminary dose expansion studies: no standard effective treatment regimen, or failure to receive standard treatment regimen, or intolerance to standard treatment regimen, or not applicable at this stage; 2)Phase IIa dose extension and fixed dose studies: Subjects with specific tumor types such as renal cell carcinoma, hepatocellular carcinoma, esophageal carcinoma, non-small cell lung cancer, etc., who have failed standard treatment, or are intolerant to standard treatment, or are currently ineligible for standard treatment (see Appendix 1 for specific inclusion criteria for each tumor type); (2)Combination studies (including stage I and IIa) : subjects with unresectable locally advanced or metastatic NSCLC and ovarian cancer (see Appendix 1 for specific inclusion criteria for each tumor type); 4.All toxicities from prior antitumor therapy were relieved to a level of grade 0-1 (according to NCI CTCAE 5.0) or acceptable by inclusion/exclusion criteria. Hair loss and other toxicities that researchers believe do not pose a safety risk to subjects are excluded; 5.Adequate organ function is defined as follows: (1)Blood system: (Without receiving blood transfusion, granulocyte colony stimulating factor (G-CSF), or other medical support within 14 days prior to initiation of study therapy), Absolute value of neutrophils (ANC) >=1.5x10^9/L; Platelet (PLT) >=100x10^9/L; Hemoglobin (Hb)>=90g/L. (2)Liver function: Total bilirubin (TBIL) 1.5x ULN)>=50ml/min (calculated according to Cockcroft-Gault formula, see Appendix 6). (4)Blood coagulation: Activated partial thrombin time (APTT) =2+, 24 hours urine protein =12 weeks; 8.According to RECIST 1.1, single agent Phase I preliminary dose extension study, combination phase I dose escalation study, single agent and combination Phase IIa study, subjects have at least one measurable lesion with no prior local treatment [acceptable prior local treatment, However, measurable lesions that were subsequently confirmed to have progressed according to RECIST V1.1 criteria were selected as targets, except for the non-small cell lung cancer cohort; only bone metastases or only CNS metastases were not accepted as measurable lesions]; 9.Fertile female subjects whose blood pregnancy results are
Exclusion criteria
Exclusion criteria: 1.Previous history of severe allergy to protein drugs or known allergy to any drug or drug component of the study drug; 2.Previous cell therapy or tumor vaccine (for IIa only); 3.See Appendix 2 for specific exclusion criteria for each tumor species in single-drug and combination studies; 4.History of hypertensive crisis or hypertensive encephalopathy; 5.History of uncorrected serum potassium, calcium or magnesium electrolyte disturbances; 6.Evidence of significant clotting disorder or other obvious bleeding risk: (1)History of intracranial hemorrhage or spinal cord hemorrhage; (2)Those with tumor lesions involving large vessels and significant risk of bleeding (e.g., central lung squamous cell carcinoma); (3)Thrombotic or embolic events or significant vascular disease (such as aortic aneurysm requiring surgical repair) within 6 months prior to the initiation of study treatment; (4)Clinically significant hemoptysis or tumor hemorrhage of any cause within 1 month prior to screening; (5)Use anticoagulant therapy for therapeutic purposes (except low-molecular-weight heparin) within 2 weeks prior to initiation of study therapy; (6)Antiplatelet agents, such as aspirin (>325 mg/ day), clopidogrel (>75 mg/ day), dipyridamole, ticlopidine, or cilostazol, were used within 10 days prior to study initiation; 7.There is a clear interstitial lung disease or non-infectious pneumonia; 8.Currently active tuberculosis; 9.Previous antiangiogenic therapy with >= grade 3 toxicity associated with antiangiogenic therapy (except for toxicities such as fever that the investigator considered did not pose a safety risk to the subjects and hypertension above grade 3); 10.Received the following treatment or medication before starting study treatment: (1)Major surgery performed within 28 days prior to the commencement of study treatment (Note: Major surgery is defined as any invasive surgery with extensive excision, such as entry into a body cavity, removal of an organ, or normal anatomical changes; If the mesothelial cell barrier (e.g., pleural cavity, peritoneum, meningeal) is opened, the operation is considered major. Biopsy for the purpose of surgery, central venous access is not major surgery) or have an unhealed wound, ulcer, or fracture. (2)Live attenuated vaccine was administered within 28 days prior to the start of study treatment. (3)Received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other antitumor drug therapy within 28 days of the first administration, except the following: 1)Nitrosorea or mitomycin c within 6 weeks before the first administration of the study drug; 2)Oral fluorouracil and small molecule targeted drugs are 2 weeks before the first use of the study drug or within the 5 half-lives of the drug (whichever is longer); 3)Chinese medicines with anti-tumor indications were used within 2 weeks before the first use of the study drug. (4)Had been treated with a systemic immune stimulant (such as interferon -a and interleukin-2) within 28 days prior to initiation of study therapy or had remained within the 5 half-life of the therapeutic agent (the older of the two); (5)Received intravenous broad-spectrum antibiotic therapy (for phase IIa only) within 2 weeks prior to initiation of study therapy; (6)Received systemic glucocorticoid (prednisone > 10mg/ day or equivalent dose of the same drug) or other immunosuppressive therapy within 14 days prior to first administration; Except for the fol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease Control Rate;overall survival; | — |
Countries
China
Contacts
Public ContactGuo Ye
Shanghai Orient Hospital
Outcome results
None listed