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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: LM-108; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alex Yuan; Phone Number: +8615901815211; Email: alexyuan@lanovamed.com
• Study Contact Backup: Name: Paul Kong; Phone Number: +8613564682439; Email: paulkong@lanovamed.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
      • Contact: Lin Shen; Phone Number: 13911219511; Email: linshenpku@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-108 in Combination with Toripalimab	Drug: LM-108; Q3W, Intravenous Drip; Drug: Toripalimab; Q3W, Intravenous Drip

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate assessed by Independent Review Committee against the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs	Incidence of adverse events	104 weeks
SAEs	Incidence of serious adverse events	104 weeks
AE/SAE	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	104 weeks
DOR	Duration of response assessed by Independent Review Committee against the RECIST v1.1	104 weeks
DCR	Disease control rate (DCR = CR + PR + SD) assessed by Independent Review Committee against the RECIST v1.1	104 weeks
PFS	Progression-free survival assessed by Independent Review Committee against the RECIST v1.1	104 weeks
Progression-free survival Rates	Independent Review Committee evaluated the Progression-free survival rates at 3 and 6 months based on RECIST v1.1	104 weeks
ORR	Overall Response Rate assessed by investigator against the RECIST v1.1	104 weeks
DOR	Duration of response assessed by investigator against the RECIST v1.1	104 weeks
DCR	Disease control rate (DCR = CR + PR + SD) assessed by investigator against the RECIST v1.1	104 weeks
PFS	Progression-free survival assessed by investigator against the RECIST v1.1	104 weeks
Progression-free survival Rates	Investigator evaluated the Progression-free survival rates at 3 and 6 months based on RECIST v1.1	104 weeks
OS	Overall survival	104 weeks
OS rates	Overall survival rates	104 weeks
Temperatures	Temperatures	104 weeks
Pulse in BPM	Beat per Minute	104 weeks
Blood Pressure	Blood Pressure in mmHg，Both systolic pressure and diastolic pressure	104 weeks
Weight	Weight in Kg	104 weeks
Height	Height in centimeter	104 weeks
Complete Blood Count		104 weeks
Urine Routine test	Laboratory tests-Urine Routine test	104 weeks
Blood biochemistry	Laboratory tests-Blood biochemistry	104 weeks
Coagulation function	Laboratory tests-Coagulation function	104 weeks
Thyroid function	Laboratory tests-Thyroid function	104 weeks
Stool routine examination	Laboratory tests-Stool routine examination	104 weeks
Virological examination	Laboratory tests-Virological examination	104 weeks
Pregnancy check	Laboratory tests-Pregnancy check	104 weeks
LVEF	Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	104 weeks
HR	Electrocardiogram (ECG) in HR	104 weeks
RR	Electrocardiogram (ECG) in RR	104 weeks
PR	Electrocardiogram (ECG) in PR	104 weeks
QRS	Electrocardiogram (ECG) in QRS	104 weeks
QT	Electrocardiogram (ECG) in QT	104 weeks
QTcF	Electrocardiogram (ECG) in QTcF	104 weeks
ECOG score	Eastern Cooperative Oncology Group score	104 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
iORR	Immune Overall Response Rate assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors	104 weeks
iDOR	Immune Duration of response assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors	104 weeks
iDCR	Immune Disease control rate assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors	104 weeks
iPFS	Immune Progression-free survival assessed by investigator according to the Immune Response Evaluation Criteria in solid Tumors	104 weeks
PK Parameter:Ctrough	PK Parameter:steady state at the end of the dosing interval Concentration	104 weeks
Immunogenicity testing	Anti-Drug antibody and Nab (if necessary) will be tested.	104 weeks
Biomarker correlation	For the detection of MSI or MMR, and CCR8 and PD-L1	104 weeks

Collaborators and Investigators

• Sponsor: LaNova Medicines Limited
• Collaborators: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 26, 2025
• Primary Completion (Estimated): January 26, 2028
• Study Completion (Estimated): January 26, 2030

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LM-108-II-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No