A Phase I/II, First-in-Human, Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM-24C5 in Patients with Advanced Solid Tumors

• Participate in any other clinical trial within 28 days prior to 1st dosing of LM-24C5.
•  Any prior treatments targeting 4-1BB and/or CEACAM5.
•  Subjects with anti-tumor treatment within 21 days prior to 1st dosing of LM-24C5, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. the following treatments have different time limits: Local small-scale palliative radiotherapy (bone metastasis radiotherapy to control pain) within 14 days prior to 1st dosing.
  • Oral anti-tumor therapy, including fluorouracil antitumor drugs and small molecular targeted drugs, etc. within 14 days or 5 half-lives of the drug (whichever is longer) prior to 1st dosing.
  • Traditional herbal medicine with anti-tumor indication within 14 days prior to 1st dosing.
  • Nitrosourea or Mitomycin C within 42 days prior to 1st dosing.
•  Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0 (Except for toxicities without safety risk judged by the investigator, such as alopecia, and other ≤ grade 2 long term toxicities).
•  Subjects with uncontrolled pain. Subjects requiring analgesic treatment must be on a stable regimen before participating in the study.
•  Subjects with known central nervous system (CNS) or meningeal metastasis.
•  Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
•  Subjects who experienced grade 3 or higher hypersensitivity to the treatment that any contains monoclonal antibody.
•  Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications (including, but not limited to, prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor agents) within 2 weeks prior to the first dosing of LM-24C5. Usage of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids is allowed.
  • Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Medical Monitor.
  • Subjects with history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments performed on MRI/CT.
  • The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency is allowed.
• Subjects with the known history of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, glomerulonephritis, etc. (see Appendix 3 for a more comprehensive list of autoimmune diseases).A history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone is allowed
•  Subjects with the history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
•  Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-24C5.
•  Subjects who are taking therapeutic doses of anticoagulants such as heparin or vitamin K antagonists for presence of active thromboembolic disease (patients on a stable anticoagulation dose for preventive of thromboembolic events due to venous thromboembolism, mechanical valves, atrial fibrillation, etc. are eligible).
•  Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-24C5 (excluding tumor biopsy, puncture, etc.).
•  Subjects who have severe cardiovascular disease, including but not limited to:
  • Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, and II-III-degree atrioventricular block, etc.
  • Thromboembolic events requiring therapeutic anticoagulation or equipped with venous filters.
  •  Cardiac insufficiency of grade III~IV according to the New York Heart Association (NYHA) standards.
  • Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months prior to 1st dosing of LM-24C5.
  • Clinically uncontrollable hypertension.
•  Subjects who have uncontrolled or severe illness, including but not limited to ongoing or active infection (e.g., active COVID-19/SARS-CoV-2 infection, etc.) requiring therapeutic antibiotics and/or other administration, while SARS-CoV-2 testing is not mandatory for study entry, and the testing should follow local clinical practice guidelines/standards.
•  Subjects who have a history of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, or organ transplantation, or allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
•  HIV infection, active infection including tuberculosis, HBV and HCV infection, with the exception:
  • If HBV infection was indicated, those with HBV DNA < 500 IU/ML (or equivalent level) and normal liver function, combined with clinical manifestations, judged by the investigator to exclude active infection are eligible.
  • If HCV infection was indicated (defined as the presence of HCV antibody), those with negative hepatitis C virus RNA test results and normal liver function are eligible.
•  Subjects who have other active malignancies which are likely to require the treatment.
•  Child-bearing potential female who have positive results in pregnancy test or are lactating.
•  Subjects who have psychiatric illness or disorders that may preclude study compliance.
•  Subject who is judged as not eligible to participate in this study by the investigator.

No restrictions