A Phase I/II Study of LM-101 Injection in Patients With Advanced Malignant Tumors

Official title

A Phase I/II, Open-label, Dose Escalation, and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of LM-101 Injection as a Single Agent or Combination Therapy in Patients With Advanced Malignant Tumors

Overview

This study is to assess the safety and tolerability, obtain Maximum Tolerated Dose (MTD) and/or the recommended phase 2 dose (RP2D) of LM-101 as a single agent or in combination in patients with advanced malignant tumors

Interventions

• Drug LM101
  Administered intravenously
• Drug Toripalimab
  Administered intravenously
• Drug Rituximab
  Administered intravenously

Primary outcome measures

• Incidence of adverse events (AEs) [Time frame: 48 weeks]
• Incidence of dose-limitingtoxicity (DLT) [Time frame: 48 weeks]
• Incidence of serious adverse event (SAE) [Time frame: 48 weeks]
• Temperature in ℃ [Time frame: 48 weeks]
• Pulse in BPM(Beat per Minute) [Time frame: 48 weeks]
• Blood Pressure in mmHg [Time frame: 48 weeks]
• Weight in Kg [Time frame: 48 weeks]
• Height in centimeter [Time frame: 48 weeks]
• Laboratory tests-Blood Routine examination [Time frame: 48 weeks]
• Laboratory tests-Urine Routine test [Time frame: 48 weeks]

Secondary outcome measures (12)

• Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) [Time frame: 112 weeks]
• PK Parameter:Time of Maximum Observed Concentration (Tmax) [Time frame: 112 weeks]
• PK Parameter: Area Under the Concentration-time Curve(AUC) [Time frame: 112 weeks]
• PK Parameter: Steady State Maximum Concentration(Cmax,ss) [Time frame: 112 weeks]
• PK Parameter: Steady State Minimum Concentration(Cmin,ss) [Time frame: 112 weeks]
• PK Parameter: Systemic Clearance at Steady State (CLss) [Time frame: 112 weeks]
• PK Parameter: Accumulation Ratio (Rac) [Time frame: 48 weeks]
• PK Parameter: Elimination Half-life (t1/2) [Time frame: 112 weeks]
• PK Parameter: Volume of Distribution at Steady-State (Vss) [Time frame: 112 weeks]
• PK Parameter: Degree of Fluctuation (DF) [Time frame: 112 weeks]
• Immunogenicity of LM-101 [Time frame: 112 weeks]
• Receptor Occupancy of LM-101 [Time frame: 48 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, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Life expectancy ≥ 3 months.
• Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and have progressed on standard therapy.
• At least one evaluable lesion.
• Subjects in the combination therapy group must have Archived Samples or fresh tumor tissue specimens are required for testing.
• Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose:
• Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception prior to study entry, during the study and for 6 months after the last dose of study drug.
• Subjects who can communicate well with investigators and understand and adhere to the requirements of this study.

Exclusion criteria

• Subject has received prior investigational therapy directed at the same target therapy.
• Subjects has participated in any other interventional clinical trial within 21 days prior to the first dosing of LM-101.
• Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-101, including radiotherapy, chemotherapy, endocrine therapy, and immunotherapy, etc.
• Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
• Poorly controlled tumor-related pain.
• Subjects with symptomatic/active central nervous system (CNS) metastases.
• Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• Subjects with known hypersensitivity to antibody therapy.
• Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medicationswithin 2 weeks prior to the first dosing of LM-101.
• Subjects with the known history of autoimmune disease with the exception of subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone.
• Subject who has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
• Use of any live attenuated vaccines within 28 days prior to the first dosing of LM-101.
• Subjects who are using therapeutic doses of anticoagulants such as heparin or vitamin K antagonists.
• Subjects who received major surgery or interventional treatment within 28 days prior to the first dosing of LM-101 (excluding tumor biopsy, puncture, etc.).
• Subjects who have history of severe cardiovascular disease.
• Subjects who have uncontrolled or severe illness.
• Subjects who have a history of immunodeficiency disease.
• HIV infection, active tuberculosis or active HBV and HCV infection.
• Subjects who have Known history of active tuberculosis.
• Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.
• Child-bearing potential female who have positive results in pregnancy test or are lactating.
• Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial.
• 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

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 5 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• Zhongnan Hospital of Wuhan University — Wuhan
• Linyi Cancer Hospital — Linyi
• Beijing Tongren Hospital, CMU — Beijing
• Fudan University Shanghai Cancer Center — Shanghai

Publications

• Cai J, Zhao B, Ji D, Zhou F, Bai S, Fang X, Nie M, Bai B, Zhang Y, Li J, Li H, Li Y, Fei D, Qin X, Qin C, Zhao S, Xia Y, Cai Q. LM-101, an Anti-SIRPalpha Antibody, in Patients with Relapsed/Refractory Lymphoma and Advanced Head and Neck Cancer: An Open-Label, Multicenter, Phase I Trial. Clin Cancer Res. 2026 Jun 15;32(12):2391-2402. doi: 10.1158/1078-0432.CCR-25-2357. PMID 41910591

Identifiers

NCT: NCT05615974 · LM101-01-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗