Advanced Solid Tumor
Conditions
Brief summary
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.
Interventions
DRUGLM-108
Q3W, Intravenous Drip
DRUGToripalimab
Q3W, Intravenous Drip
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
LaNova Medicines Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 104 weeks | Overall Response Rate assessed by Independent Review Committee against the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | 104 weeks | Blood Pressure in mmHg，Both systolic pressure and diastolic pressure |
| HR | 104 weeks | Electrocardiogram (ECG) in HR |
| RR | 104 weeks | Electrocardiogram (ECG) in RR |
| PR | 104 weeks | Electrocardiogram (ECG) in PR |
| QRS | 104 weeks | Electrocardiogram (ECG) in QRS |
| QT | 104 weeks | Electrocardiogram (ECG) in QT |
| QTcF | 104 weeks | Electrocardiogram (ECG) in QTcF |
| ECOG score | 104 weeks | Eastern Cooperative Oncology Group score |
| AEs | 104 weeks | Incidence of adverse events |
| SAEs | 104 weeks | Incidence of serious adverse events |
| AE/SAE | 104 weeks | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |
| DOR | 104 weeks | Duration of response assessed by Independent Review Committee against the RECIST v1.1 |
| DCR | 104 weeks | Disease control rate (DCR = CR + PR + SD) assessed by Independent Review Committee against the RECIST v1.1 |
| PFS | 104 weeks | Progression-free survival assessed by Independent Review Committee against the RECIST v1.1 |
| Progression-free survival Rates | 104 weeks | Independent Review Committee evaluated the Progression-free survival rates at 3 and 6 months based on RECIST v1.1 |
| ORR | 104 weeks | Overall Response Rate assessed by investigator against the RECIST v1.1 |
| OS | 104 weeks | Overall survival |
| OS rates | 104 weeks | Overall survival rates |
| Temperatures | 104 weeks | Temperatures |
| Pulse in BPM | 104 weeks | Beat per Minute |
| Weight | 104 weeks | Weight in Kg |
| Height | 104 weeks | Height in centimeter |
| Complete Blood Count | 104 weeks | — |
| Urine Routine test | 104 weeks | Laboratory tests-Urine Routine test |
| Blood biochemistry | 104 weeks | Laboratory tests-Blood biochemistry |
| Coagulation function | 104 weeks | Laboratory tests-Coagulation function |
| Thyroid function | 104 weeks | Laboratory tests-Thyroid function |
| Stool routine examination | 104 weeks | Laboratory tests-Stool routine examination |
| Virological examination | 104 weeks | Laboratory tests-Virological examination |
| Pregnancy check | 104 weeks | Laboratory tests-Pregnancy check |
| LVEF | 104 weeks | Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage |
Other
| Measure | Time frame | Description |
|---|---|---|
| iDCR | 104 weeks | Immune Disease control rate assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors |
| iPFS | 104 weeks | Immune Progression-free survival assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors |
| PK Parameter:Ctrough | 104 weeks | PK Parameter:steady state at the end of the dosing interval Concentration |
| Immunogenicity testing | 104 weeks | Anti-Drug antibody and Nab (if necessary) will be tested. |
| Biomarker correlation | 104 weeks | For the detection of MSI or MMR, and CCR8 and PD-L1 |
| iORR | 104 weeks | Immune Overall Response Rate assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors |
| iDOR | 104 weeks | Immune Duration of response assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors |
Countries
China
Contacts
Primary ContactAlex Yuan
Backup ContactPaul Kong
Outcome results
None listed