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

Official title

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

Overview

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.

Interventions

• Drug LM-168
  Q3W,Intravenous Drip
• Drug Toripalimab
  Q3W,Intravenous

Primary outcome measures

• Incidence of adverse events (AEs) [Time frame: 78 weeks]
• Incidence of dose-limitingtoxicity (DLT) [Time frame: 78 weeks]
• Incidence of serious adverse event (SAE) [Time frame: 78 weeks]
• Temperature (Celsius) [Time frame: 78 weeks]
• Pulse in BPM(Beat per Minute) [Time frame: 78 weeks]
• Blood Pressure in mmHg [Time frame: 78 weeks]
• Weight in Kg [Time frame: 78 weeks]
• Height in centimeter [Time frame: 78 weeks]
• Blood Routine examination [Time frame: 78 weeks]
• Urine Routine test [Time frame: 78 weeks]

Secondary outcome measures (12)

• Objective Response Rate (ORR) [Time frame: 78 weeks]
• Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) [Time frame: 130 weeks]
• PK Parameter:Time of Maximum Observed Concentration (Tmax) [Time frame: 130 weeks]
• PK Parameter: Area Under the Concentration-time Curve(AUC) [Time frame: 130 weeks]
• PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss) [Time frame: 130 weeks]
• PK Parameter: Steady State Minimum Concentration(Cmin,ss) [Time frame: 130 weeks]
• PK Parameter: Systemic Clearance at Steady State (CLss) [Time frame: 130 weeks]
• PK Parameter: Accumulation Ratio (Rac) [Time frame: 130 weeks]
• PK Parameter: Elimination Half-life (t1/2) [Time frame: 130 weeks]
• PK Parameter: Volume of Distribution at Steady-State (Vss) [Time frame: 130 weeks]
• PK Parameter: Degree of Fluctuation (DF) [Time frame: 130 weeks]
• Immunogenicity testing [Time frame: 130 weeks]

Eligibility criteria

Inclusion criteria

• Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
• Aged ≥18 years old (including boundary values) , male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥ 3 months.
• 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.
• In dose expansion stage, subjects must have histological or cytological confirmation of selected advanced solid tumors.
• Pre-treatment archived tumour tissue or on-treatment tumour biopsy could be provided for biomarker analysis optionally.
• At least one measurable disease.
• Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose.
• Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

Exclusion criteria

• Participate in any other clinical trial within 28 days prior to 1st dosing of LM-168.
• 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.
• Subjects who have received the anti-tumor treatments within the specified time periods prior to the first dosing of LM-168.
• Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
• Subjects with uncontrolled tumour-related pain.
• Subjects with known central nervous system (CNS) or meningeal metastasis.
• Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• Subjects with esophageal or gastric varices requiring immediate intervention, or those with a history of variceal bleeding.
• Hepatic encephalopathy, hepatorenal syndrome, Child-Pugh class B or more severe liver cirrhosis.
• Tumor invasion of surrounding vital organs or a risk of developing esophagotracheal fistula or esophagopleural fistula.
• Patients with a history of active or previously confirmed inflammatory bowel disease.
• Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains monoclonal antibody.
• 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.
• 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.
• Subjects with the known history of autoimmune disease.
• 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.
• Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-168.
• Current or recent use of aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol.
• Current unstable of full-dose oral or parenteral anticoagulants or thrombolytic agents for > 2 weeks prior to the first dose of LM-168.
• Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-168 (excluding tumour biopsy, puncture, etc.).
• Subjects who have severe cardiovascular disease.
• Subjects who have uncontrolled or severe illness.
• Subjects who have a history of immunodeficiency disease.
• HIV infection, active infection including tuberculosis, HBV and HCV infection.
• Subjects with a history of other malignancies within 5 years prior to the first administration of the study drug.
• Child-bearing potential female who have positive results in pregnancy test or are lactating.
• Subjects who have psychiatric illness or disorders that may preclude study compliance.
• Subject who is judged as not eligible to participate in this study by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 5 centers

• Macquarie University — Ryde
• MUPharm Pty Limited trading as Macquarie University Hospital Parmarcy — Ryde
• Cancer Care Wollongong Pty Limited — Wollongong
• Bayview Health-Investigational Drug Services — Perth
• One Clinical Reasearch — Perth

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT06868199 · LM168-01-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗