Advanced solid tumors
Conditions
Interventions
Group 1:PM1003 injection 0.02 mg/kg
Group 2:PM1003 injection 0.1 mg/kg
Group 3:PM1003 injection 0.3 mg/kg
Group 4:PM1003 injection 1 mg/kg
Group 5:PM1003 injection 3 mg/kg
Group 6:PM1003 injection 10 mg/kg
Group 7:PM1003 injection 20 mg/kg
Sponsors
Shanghai Orient Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in clinical study; fully understand the study and sign informed consent voluntarily; willing to follow and able to complete all test procedures; 2. Male or female aged 18 to 75 years; 3. Subjects with malignant tumor confirmed by histology or cytology; (1) Phase I dose escalation and dose expension or phase IIa fixed dosing study: subjects with advanced malignant solid tumors who have no standard treatment, have failed standard treatment, are intolerant to standard treatment, or are not eligible for standard treatment; (2) Phase IIa dose expension study: subjects with advanced solid tumors, such as non-small cell lung cancer(cohort 1: have received Immune checkpoint inhibitors; cohort 2: without the treatment with Immune checkpoint inhibitors), endometrial carcinoma, cervical cancer, urothelial carcinoma, head and neck squamous carcinoma, triple negative breast cancer, who have no standard treatment, have failed standard treatment, are intolerant to standard treatment, or are not eligible for standard treatment; 4. All acute toxicity from prior antitumor therapy is reduced to level 0-1 or to an acceptable level for inclusion/exclusion criteria; 5. Adequate organ function; 6. ECOG score was 0-1; 7. Expected survival >= 12 weeks; 8. For the phase I dose expension or phase IIa study, should have at least 1 measurable lesion that has not been previously treated locally, according to RECIST 1.1 criteria; 9. Pre-menopausal female subjects with negative blood pregnancy results within 7 days prior to the study treatment, and agree to abstain from sex or use medically approved effective contraceptive measures for 6 months from the date of signing the informed consent form to the end of the last medication; 10. Male subjects are agree to abstain from sex or use medically approved effective contraceptive methods for 6 months from the date of signing the informed consent form to the end of the last medication, and do not donate sperm during this period; 11. For the phase IIa study,subjects shall provide tumor tissue specimens for PD-L1 analysis.
Exclusion criteria
Exclusion criteria: 1. History of severe allergic to macromolecular protein drugs, severe allergy to drugs or known allergy to any component of the drug in this study; 2. Treatment with any 4-1BB monoclonal antibody or 4-1BB-containing dual antibody immune co-stimulatory molecule agonist; 3. Have hepatitis (non-alcoholic steatohepatitis, alcoholic or autoimmune hepatitis) or cirrhotic disease; 4. Known cerebrospinal membrane metastases, or uncontrolled or symptomatic central nervous system (CNS) metastases; 5. Present with definite interstitial lung disease or non-infectious pneumonia, except those caused by local radiotherapy; 6. Current active infection requiring intravenous anti-infective therapy; 7. Current presence of uncontrolled pleural, pericardial, and peritoneal effusions; 8. Presence of any active autoimmune disease or history of autoimmune disease with anticipated relapse; 9. Severe non-healing wounds/ulcers/fractures within 4 weeks prior to study trentment; 10. The following conditions within 6 months prior to initiation of trial treatment: myocardial infarction, severe/unstable angina, clinically significant arrhythmia requiring clinical intervention, cerebrovascular accident/stroke, subarachnoid hemorrhage; 11. Previous other active malignancies within 5 years prior to initiation of trial treatment, except locally treatable and cured malignancies (e.g., basal cell or squamous cell carcinoma of the skin, superficial or non-invasive bladder cancer, carcinoma in situ of the cervix, intraductal carcinoma in situ of the breast, papillary thyroid cancer) (for phase IIa); 12. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 13. Prior to initiation of trial treatment, the presence of: (1) Congenital long QT syndrome; (2) Use of a pacemaker; (3) Left ventricular ejection fraction (LVEF) 450 ms in women and > 470 ms in men (QTcF = QT/[RR^0.33]); (5) Poorly controlled diabetes mellitus (fasting glucose >= 13.3 mM); (6) Poorly controlled hypertension (systolic blood pressure >= 160 mmHg and/or diastolic blood pressure >= 95 mmHg); (7) New York Heart Association (NYHA) classification >= II cardiac insufficiency; 14. Received intravenous antibiotic therapy within 2 weeks prior to initiation of trial treatment; 15. Received unmarketed study drugs within 4 weeks prior to starting study treatment; 16. Received immunosuppressive drug therapy (such as corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-TNF-alpha drugs) within 2 weeks prior to the study treatment; 17. Received systemic immunostimulant therapy (such as interferon-alpha, interleukin-2) within 28 days prior to the study treatment or are still within 5 half-lives of the therapeutic drug (whichever is longer); 18. Have had major surgery within 4 weeks prior to the study treatment; 19. Received live attenuated vaccine within 4 weeks prior to the study treatment; 20. Received antitumor therapy such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy, etc. within 4 weeks before starting trial treatment; received nitrosourea or mitomycin C within 6 weeks before starting trial treatment; received oral fluorouracil-based and small molecule-targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) before starting trial treatment; received herbal therapy with antitumor indications within 2 weeks before starting trial treatmen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of DLT(dose limited toxicity) within 21 days after the first dose;ORR(Objective Response Rate);Severity and incidence of treatment-related adverse events (TRAEs);Anti-tumor efficacy; | — |
Secondary
| Measure | Time frame |
|---|---|
| MTD(Maximal Tolerable Dose);Pharmaco Kinetics;Immunogenicity; | — |
Countries
China
Contacts
Public ContactGuo Ye
Shanghai Orient Hospital
Outcome results
None listed