Advanced Solid Tumor
Conditions
Brief summary
This study is to assess the safety and tolerability, obtain the recommended phase 2 dose(RP2D)/or Maximum Tolerated Dose (MTD) for LM-2417 as a single agent or in combination with other anti-tumour agents in subjects with advanced solid tumours.
Interventions
DRUGLM-2417
Q2W/Q3W,Intravenous Drip
DRUGDocetaxel
Q3W,Intravenous Drip
DRUGToripalimab/Tirelizumab
Q3W,Intravenous Drip
DRUGCarboplatin
Q3W,Intravenous Drip
DRUGNiraparib
QD,Oral Administration
DRUGLenvatinib
QD,Oral Administration
Sponsors
LaNova Medicines Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure. 2. Aged 18-80 years old (including boundary values) , male or female. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Life expectancy ≥ 3 months. 5. Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, or currently lack or are intolerant of, standard therapy. 6. Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing. 7. At least one evaluable lesion. 8. Subjects must show appropriate organ and marrow function inlaboratory examinations within 7 days prior to the first dose. 9. Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception prior to study entry, during the study and for 6 months after the last dose of study drug. 10. Subjects who can communicate well with investigators and understand and adhere to the requirements of this study. Single-agent dose of 6mg/kg, 12mg/kg and and combined cohort：Subjects tested positive for biomarkers.
Exclusion criteria
1. Previously received with same target therapy. 2. Subjects has participated in any other interventional clinical trial within 28 days prior to the first dosing of LM-2417. 3. Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-2417, including radiotherapy, chemotherapy, endocrine therapy, and immunotherapy, etc. 4. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0. 5. Poorly controlled tumor-related pain. 6. Subjects with symptomatic/active central nervous system (CNS)metastases. 7. Subject who have uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 8. Subjects with known hypersensitivity to antibody therapy; 9. Subjects who take systemic corticosteroids (\> 10 mg daily prednisone equivalents) for more than 7 days or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of LM-2417. 10. Previous or current known autoimmune disease. 11. Subject who has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. 12. Use of any live vaccine or live attenuated vaccines within 28 days prior to the first dosing of LM-2417.; 13. Subjects who are using therapeutic doses of anticoagulants such as heparin or vitamin K antagonists. 14. Subjects who received major surgery or interventional treatment within28 days prior to the first dosing of LM-2417. 15. Subject who have history of severe cardiovascular disease. 16. Subjects who have uncontrolled or severe illness. 17. HIV infection, active HBV or HCV infection. 18. Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening. 19. Child-bearing potential female who have positive results in pregnancy test or are lactating. 20. Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial. 21. Subject who is judged as not eligible to participate in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulse in BPM(Beat per Minute) | 60 weeks | Phase I/II |
| Blood Pressure in mmHg | 60 weeks | Phase I/II |
| Weight in Kg | 60 weeks | Phase I/II |
| Height in centimeter | 60 weeks | Phase I/II |
| Laboratory tests-Blood Routine examination | 60 weeks | Phase I/II |
| Laboratory tests-Urine Routine test | 60 weeks | Phase I/II |
| Laboratory tests-Blood biochemistry | 60 weeks | Phase I/II |
| Laboratory tests- Coangulation function | 60 weeks | Phase I/II |
| Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in HR | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in RR | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in PR | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in QRS | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in QT | 60 weeks | Phase I/II |
| 12-lead electrocardiogram (ECG) in QTcF | 60 weeks | Phase I/II |
| ECOG(Eastern Cooperative Oncology Group) score | 60 weeks | Phase I/II |
| Overall Response Rate (ORR) | 76 weeks | Phase I/II |
| Incidence of adverse events (AEs) | 60 weeks | Phase I/II |
| Incidence of dose-limitingtoxicity (DLT) | 60 weeks | Phase I/II |
| Incidence of serious adverse event (SAE) | 60 weeks | Phase I/II |
| Temperatures | 60 weeks | Phase I/II |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) | 112 weeks | Phase I/II |
| PK Parameter: Systemic Clearance at Steady State (CLss) | 112 weeks | Phase I/II |
| PK Parameter: Accumulation Ratio (Rac) | 112 weeks | Phase I/II |
| PK Parameter: Elimination Half-life (t1/2) | 112 weeks | Phase I/II |
| PK Parameter: Volume of Distribution at Steady-State (Vss) | 112 weeks | Phase I/II |
| PK Parameter: Degree of Fluctuation (DF) | 112 weeks | Phase I/II |
| Immunogenicity of LM-2417 | 112 weeks | Phase I/II |
| Biomarker correlation(NaPi2b) | 112 weeks | Phase I/II |
| Duration of Response (DOR) in Month | 64 weeks | Phase I/II |
| Disease control rate (DCR) in percentage | 64 weeks | Phase I/II |
| progression-free survival (PFS) in Month | 64 weeks | Phase I/II |
| Safety: AE/SAE (Number of participants with treatment-related adverse events as Overall survival (OS) in Month | 64 weeks | Phase I/II |
| Changes of target lesions from baseline in Millimeter | 64 weeks | Phase I/II |
| AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) | 64 weeks | Phase I/II |
| PK Parameter:Time of Maximum Observed Concentration (Tmax) | 112 weeks | Phase I/II |
| PK Parameter: Area Under the Concentration-time Curve(AUC) | 112 weeks | Phase I/II |
| PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss) | 112 weeks | Phase I/II |
| PK Parameter: Steady State Minimum Concentration(Cmin,ss) | 112 weeks | Phase I/II |
Countries
China
Contacts
CONTACTLingli Zhao
CONTACTPaul Kong
Outcome results
None listed