A Study of LM-168 as a Single Agent or in Combination With Toripalimab in Subjects With Advanced Solid Tumours

Phase 1

Not yet recruiting

• Conditions: Advanced Solid Tumours
• Interventions: Drug: LM-168; Drug: Toripalimab

• Registration Number: NCT06868199
• Lead Sponsor: LaNova Medicines Limited

Brief Summary

For phase I ,this study is to assess the safety and tolerability, obtain the recommended phase 2 dose (RP2D) and/or Maximum Tolerated Dose (MTD) for LM-168 as a single agent or in combination with toripalimab in subjects with advanced solid tumours.

For phase II ,this study is to assess the preliminary anti-tumour activity of LM-168 as a single agent or in combination with toripalimab measured by objective response rate (ORR) in subjects with advanced solid tumours.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-06
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-04
• Last Update Submitted: 2025-03-04
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10
• Study Start: 2025-03-31
• Primary Completion: 2027-08-01
• Study Completion: 2028-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

1. Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
2. Aged ≥18 years old (including boundary values) , male or female.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Life expectancy ≥ 3 months.
5. In dose escalation stage, subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumours, and have progressed on standard therapy, or are intolerable for available standard therapy, or there is no available standard therapy.
6. In dose expansion stage, subjects must have histological or cytological confirmation of selected advanced solid tumors.
7. Pre-treatment archived tumour tissue or on-treatment tumour biopsy could be provided for biomarker analysis optionally.
8. At least one measurable disease.
9. Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose.
10. Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

Exclusion Criteria

1. Participate in any other clinical trial within 28 days prior to 1st dosing of LM-168.
2. Having received prior the same target or any other immunotherapy or immune-oncology (IO) agent within 28 days of commencing treatment with LM-168.
3. Subjects who have received the anti-tumor treatments within the specified time periods prior to the first dosing of LM-168.
4. Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
5. Subjects with uncontrolled tumour-related pain.
6. Subjects with known central nervous system (CNS) or meningeal metastasis.
7. Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
8. Subjects with esophageal or gastric varices requiring immediate intervention, or those with a history of variceal bleeding.
9. Hepatic encephalopathy, hepatorenal syndrome, Child-Pugh class B or more severe liver cirrhosis.
10. Tumor invasion of surrounding vital organs or a risk of developing esophagotracheal fistula or esophagopleural fistula.
11. Patients with a history of active or previously confirmed inflammatory bowel disease.
12. Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains monoclonal antibody.
13. Subjects who previously experienced grade ≥ 3 immune-related adverse events during immunotherapy, as well as subjects who discontinued prior immunotherapy due to severe or life-threatening immune-related adverse events.
14. Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of LM-168.
15. Subjects with the known history of autoimmune disease.
16. Subjects with the history of idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, interstitial lung disease, severe radiation pneumonitis or evidence of active pneumonitis on screening chest CT scan.
17. Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-168.
18. Current or recent use of aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol.
19. Current unstable of full-dose oral or parenteral anticoagulants or thrombolytic agents for > 2 weeks prior to the first dose of LM-168.
20. Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-168 (excluding tumour biopsy, puncture, etc.).
21. Subjects who have severe cardiovascular disease.
22. Subjects who have uncontrolled or severe illness.
23. Subjects who have a history of immunodeficiency disease.
24. HIV infection, active infection including tuberculosis, HBV and HCV infection.
25. Subjects with a history of other malignancies within 5 years prior to the first administration of the study drug.
26. Child-bearing potential female who have positive results in pregnancy test or are lactating.
27. Subjects who have psychiatric illness or disorders that may preclude study compliance.
28. Subject who is judged as not eligible to participate in this study by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LM-168 Dose Escalation	LM-168	-
LM-168 Dose Expansion	LM-168	-
LM-168 combination dose escalation	LM-168	-
LM-168 combination dose escalation	Toripalimab	-
LM-168 combination dose expansion	LM-168	-
LM-168 combination dose expansion	Toripalimab	-

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs)	78 weeks	Phase I
Incidence of dose-limitingtoxicity (DLT)	78 weeks	Phase I
Incidence of serious adverse event (SAE)	78 weeks	Phase I
Temperature (Celsius)	78 weeks	Phase I
Pulse in BPM(Beat per Minute)	78 weeks	Phase I
Weight in Kg	78 weeks	Phase I
Blood Pressure in mmHg	78 weeks	Phase I
Height in centimeter	78 weeks	Phase I
Blood Routine examination	78 weeks	Phase I
Urine Routine test	78 weeks	Phase I
Coangulation function test	78 weeks	Phase I
Thyroid function test	78 weeks	Phase I
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	78 weeks	Phase I
12-lead electrocardiogram (ECG) in HR	78 weeks	Phase I
12-lead electrocardiogram (ECG) in QT	78 weeks	Phase I
12-lead electrocardiogram (ECG) in RR	78 weeks	Phase I
12-lead electrocardiogram (ECG) in PR	78 weeks	Phase I
12-lead electrocardiogram (ECG) in QRS	78 weeks	Phase I
12-lead electrocardiogram (ECG) in QTcF	78 weeks	Phase I
ECOG(Eastern Cooperative Oncology Group) score	78 weeks	Phase I
Objective Response Rate (ORR)	From 78th week to 130th week (52 weeks in total)	Phase II
Blood biochemistry test	78 weeks	Phase I

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	78 weeks	Phase I
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)	130 weeks	Phase I/II
PK Parameter:Time of Maximum Observed Concentration (Tmax)	130 weeks	Phase I/II
PK Parameter: Area Under the Concentration-time Curve(AUC)	130 weeks	Phase I/II
PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss)	130 weeks	Phase I/II
progression-free survival (PFS) in Month	130 weeks	Phase I/II
PK Parameter: Steady State Minimum Concentration(Cmin,ss)	130 weeks	Phase I/II
PK Parameter: Elimination Half-life (t1/2)	130 weeks	Phase I/II
PK Parameter: Systemic Clearance at Steady State (CLss)	130 weeks	Phase I/II
Disease control rate (DCR) in percentage	130 weeks	Phase I/II
PK Parameter: Accumulation Ratio (Rac)	130 weeks	Phase I/II
PK Parameter: Volume of Distribution at Steady-State (Vss)	130 weeks	Phase I/II
Duration of Response (DOR) in Month	130 weeks	Phase I/II
Changes of target lesions from baseline in Millimeter	130 weeks	Phase I/II
PK Parameter: Degree of Fluctuation (DF)	130 weeks	Phase I/II
Immunogenicity testing	130 weeks	Phase I/II
Temperature (Celsius)	From 78th week to 130th week (52 weeks in total)	Phase II
Pulse in BPM(Beat per Minute)	From 78th week to 130th week (52 weeks in total)	Phase II
Blood Pressure in mmHg	From 78th week to 130th week (52 weeks in total)	Phase II
Weight in Kg	From 78th week to 130th week (52 weeks in total)	Phase II
Height in centimeter	From 78th week to 130th week (52 weeks in total)	Phase II
Blood Routine examination	From 78th week to 130th week (52 weeks in total)	Phase II
Urine Routine test	From 78th week to 130th week (52 weeks in total)	Phase II
Blood biochemistry test	From 78th week to 130th week (52 weeks in total)	Phase II
Coangulation function test	From 78th week to 130th week (52 weeks in total)	Phase II
Thyroid function test	From 78th week to 130th week (52 weeks in total)	Phase II
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	From 78th week to 130th week (52 weeks in total)	Phase II
ECOG(Eastern Cooperative Oncology Group) score	From 78th week to 130th week (52 weeks in total)	Phase II

Trial Locations

Locations (2)

Cancer Care Wollongong; 🇦🇺 Wollongong, New South Wales, Australia

Sunshine Coast University Private Hospital; 🇦🇺 Birtinya, Queensland, Australia