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

A Phase I/II, First-in-Human (FIH), Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-168 as a Single Agent or in Combination With Toripalimab in Subjects With Advanced Solid Tumours

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumours
• Intervention / Treatment: Drug: LM-168; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 87
• Phase: Phase 2; Phase 1

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

• Australia
  • New South Wales
    • Ryde, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University
      • Contact: Andrew Parsonson, Dr; Phone Number: 0298122956; Email: andrew.parsonson@mqhealth.org.au
    • Ryde, New South Wales, Australia, 2109
      • Recruiting
      • MUPharm Pty Limited trading as Macquarie University Hospital Parmarcy
      • Contact: Andrew Parsonson, Dr; Phone Number: 0298122956; Email: andrew.parsonson@mqhealth.org.au
    • Wollongong, New South Wales, Australia
      • Recruiting
      • Cancer Care Wollongong Pty Limited
      • Contact: Udit Nindra, Dr; Email: UNindra@cancercarewollongong.com.au
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Bayview Health-Investigational Drug Services
      • Contact: Muhammad Usman Hakeem, Dr; Phone Number: 0862799466; Email: usman.hakeem@oneclinicalresearch.com.au
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Reasearch
      • Contact: Muhammad Usman Hakeem, Dr; Phone Number: 0862799466; Email: usman.hakeem@oneclinicalresearch.com.au
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Not yet recruiting
      • Beijing Cancer Hospital
      • Contact: Lin Shen, Dr; Phone Number: 13564682439; Email: paulkong@lanovamed.com

Participation Criteria

Eligibility Criteria

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

Description

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 anti-CTLA-4 or any other immunotherapy or immune-oncology (IO) agent within 28 days of commencing treatment with LM-168 or experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-168 Dose Escalation	Drug: LM-168; Q3W,Intravenous Drip
Experimental: LM-168 Dose Expansion	Drug: LM-168; Q3W,Intravenous Drip
Experimental: LM-168 combination dose escalation	Drug: LM-168; Q3W,Intravenous Drip; Drug: Toripalimab; Q3W,Intravenous
Experimental: LM-168 combination dose expansion	Drug: LM-168; Q3W,Intravenous Drip; Drug: Toripalimab; Q3W,Intravenous

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: LaNova Medicines Limited
• Investigators: Study Director: Sherry Qin, LaNova Medicines Limited

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 10, 2025

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; toripalimab
• Other Study ID Numbers: LM168-01-101

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No