A Study of LM-108 in Combination With Toripalimab in Subjects With Advanced Solid Tumours

Inclusion criteria

• Subjects with advanced solid tumors diagnosed by pathology have evidence of advanced stage or metastasis that cannot be surgically removed. And the MSI-H status will be confirmed by central laboratory designated of the sponsor.
• Aged 18.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• At least one measurable lesion.
• Subjects who have failed previous monotherapy with anti-PD-1/PD-L1 drugs or combination (synchronous or sequential) with other systemic treatments and unresectable or metastatic late stage MSI-H/dMMR solid tumors.
• Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing.
• Any adverse event from prior anti-tumor therapy and surgery has recovered to ≤ grade 1 of CTCAE v5.0.
• Subjects must show appropriate organ and marrow function in laboratory examinations.
• Women of childbearing potential (WOCBP) and Male participants must agree to use one medically recognized contraceptive measures of contraception, during the study and for 6 months after the last dose of study drug.
• Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.

Exclusion criteria

• Subjects with symptomatic/active central nervous system (CNS) metastases.
• Subject who have uncontrollable pleural effusion, pericardial effusion, and ascites despite treatment such as puncture and drainage Within 14 days prior to enrollment; Pericardial effusion accompanied by clinical symptoms or moderate or above.
• Subjects' weight decreased by more than 20% within the first 2 months of enrollment.
• Poorly controlled tumor-related pain.
• Subjects who received anti-tumour treatment, , major surgery, immunosuppressive drugs and live attenuated vaccines before enrollment.
• Subjects have received anti-tumor immunotherapy and experienced ≥ grade 3 immune related adverse events (irAE) or ≥ grade 2 immune related myocarditis.
• Subjects who have other cancers within 5 years prior to entering the research.
• Previous or current known autoimmune disease.
• Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies; Arterial/venous thrombotic events that occurred within the first 6 months of enrollment.
• Present peripheral neuropathy of grade>1 .
• Subjects who have a history of gastrointestinal perforation and/or gastrointestinal fistula within the 6 months prior to enrollment.
• Subjects who have been clinical signs or symptoms of intestinal obstruction and/or gastrointestinal obstruction Within 6 months prior to starting the study treatment.
• Presence of interstitial lung disease, non infectious pneumonia, or uncontrolled systemic diseases.
• Known to be allergic to the investigational drug or any of its excipients; Or have experienced severe allergic reactions to other monoclonal antibodies.
• HIV infection, active HBV or HCV infection.
• Subject who have clinical symptoms or diseases of the heart that have not been well controlled.
• Subjects who take Systemic use of antibiotics for more than 7 days within the first 4 weeks prior to enrollment, or unexplained fever>38.5 ° C during screening/before first administration .
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Subjects who have participated in any other drug clinical studies within 4 weeks prior to enrollment, or have not exceeded 5 half lives since the last study medication.
• Known history of abuse or drug use of psychotropic substances.
• Subjects who have other serious physical or mental illnesses or laboratory abnormalities and judged as not eligible to participate in this study by the investigator.