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

Evaluation of a Phase II, Single-arm, Multicenter, Open-label Clinical Study on LM-108 Injection in Combination With Toripalimab for Advanced Malignant Solid Tumors in Patients With Unresectable or Metastatic Microsatellite Highly Unstable (MSI H) or Mismatch Repair Defects (dMMR) Who Have Failed Previous Treatment With Anti-PD-1/PD-L1 Drugs

Based on overall response rate (ORR) as assessed by the Independent Review Committee (IRC) against the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria for Solid Tumor Efficacy, To evaluate the efficacy of LM-108 in combination with Toripalimab in patients with advanced malignant solid tumours with unresectable or metastatic MSI-H/dMMR who have failed previous anti-PD-1 /PD-L1 therapy.

Inclusion Criteria:

1. 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.
2. Aged 18.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. At least one measurable lesion.
5. 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.
6. Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing.
7. Any adverse event from prior anti-tumor therapy and surgery has recovered to ≤ grade 1 of CTCAE v5.0.
8. Subjects must show appropriate organ and marrow function in laboratory examinations.
9. 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.
10. Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.

Exclusion Criteria:

1. Subjects with symptomatic/active central nervous system (CNS) metastases.
2. 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.
3. Subjects' weight decreased by more than 20% within the first 2 months of enrollment.
4. Poorly controlled tumor-related pain.
5. Subjects who received anti-tumour treatment, , major surgery, immunosuppressive drugs and live attenuated vaccines before enrollment.
6. Subjects have received anti-tumor immunotherapy and experienced ≥ grade 3 immune related adverse events (irAE) or ≥ grade 2 immune related myocarditis.
7. Subjects who have other cancers within 5 years prior to entering the research.
8. Previous or current known autoimmune disease.
9. 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.
10. Present peripheral neuropathy of grade>1 .
11. Subjects who have a history of gastrointestinal perforation and/or gastrointestinal fistula within the 6 months prior to enrollment.
12. Subjects who have been clinical signs or symptoms of intestinal obstruction and/or gastrointestinal obstruction Within 6 months prior to starting the study treatment.
13. Presence of interstitial lung disease, non infectious pneumonia, or uncontrolled systemic diseases.
14. Known to be allergic to the investigational drug or any of its excipients; Or have experienced severe allergic reactions to other monoclonal antibodies.
15. HIV infection, active HBV or HCV infection.
16. Subject who have clinical symptoms or diseases of the heart that have not been well controlled.
17. 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 .
18. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
19. 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.
20. Known history of abuse or drug use of psychotropic substances.
21. 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.