A Study of LM-350 in Subjects With Advanced Solid Tumours

Official title

A Phase I/II, First-in-Human (FIH), Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM-350 in Patients With Advanced Solid Tumors

Overview

For Phase I Dose Escalation Stage, to assess the safety and tolerability of LM-350 in patients with advanced solid tumors,determine the maximum tolerated dose (MTD) or optimal biological dose (OBD), and explore the relationship between the biomarkers and the anti-tumor activity of LM-350. For Phase II Dose Expansion Stage, to assess the preliminary anti-tumor activity of LM-350 in patients with advanced solid tumors.

Interventions

• Drug LM-350 for injection
  Q3W,Intravenous Drip

Primary outcome measures

• Incidence of dose-limitingtoxicity (DLT) [Time frame: 78 weeks]
• Incidence of Treatment-Emergent Adverse Events (AEs) [Time frame: 78 weeks]
• Incidence of serious adverse events (SAEs) [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 -> Complete Blood Count [Time frame: 78 weeks]
• Urine Routine examination ->Urinalysis [Time frame: 78 weeks]

Secondary outcome measures (12)

• 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->Anti-Drug Antibody test [Time frame: 130 weeks]
• Objective Response Rate (ORR) [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.
• Participant must be ≥18 years or the legal age of consent at the time of signing the ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥ 3 months.
• Patients with advanced solid tumors confirmed by histopathological diagnosis who have failed standard treatment, are intolerant to standard treatment, or for whom standard treatment is currently unsuitable.
• Pre-treatment archived tumour tissue (within 3 years) or on-treatment tumour biopsy could be provided for biomarker analysis.
• Must have at least one measurable lesion according to RECIST v1.1.
• Adequate organ and bone marrow function as defined by protocol.
• 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-350.
• Subjects who have received treatment with the same targeting.
• History of ≥ Grade 3 late diarrhea during or after previous treatment with a topoisomerase inhibitor.
• Subjects who have received the following anti-tumor treatments within the specified time periods prior to the first dosing of LM-350.
• 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 clinically uncontrollable third-space fluid accumulation.
• Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains monoclonal antibody.
• Subjects who take systemic corticosteroids (≥ 10 mg/day of prednisone or equivalents) or other systemic immunosuppressive medications within 2 weeks prior to the first dose of LM-350.
• Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses, and any autoimmune, or prior pneumonectomy.
• Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-350.
• Current unstable of full-dose oral or parenteral anticoagulants or thrombolytic agents for > 2 weeks prior to the first dose of LM-350.
• Subjects with active or a documented history of chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease).
• Subjects with complete or incomplete intestinal obstruction within 3 months prior to the first dose of the study drug , orpatients who are currently at the risk of intestinal perforation.
• Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-350.
• 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 who have other active malignancies which are likely to require the treatment.
• 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

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 3 centers

• Cancer Care Wollongong Pty Limited — Wollongong
• Cancer Research SA — Adelaide
• Peninsula and South Eastern Haematology and Oncology Group — Frankston

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT07112222 · LM350-01-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗