A Phase I/II Study of LM-2417 in Subjects With Advanced Solid Tumours

Official title

An Open-label, Dose-escalation, and Dose-expansion Phase I/II Clinical Study of Safety, Tolerability, Pharmacokinetic Profile, and Initial Efficacy of LM-2417 for Injection Alone or in Combination With Other Antitumor Agents in Patients With Advanced Solid Tumors

Overview

This study is to assess the safety and tolerability, obtain the recommended phase 2 dose(RP2D)/or Maximum Tolerated Dose (MTD) for LM-2417 as a single agent or in combination with other anti-tumour agents in subjects with advanced solid tumours.

Interventions

• Drug LM-2417
  Q2W/Q3W,Intravenous Drip
• Drug Docetaxel
  Q3W,Intravenous Drip
• Drug Toripalimab/Tirelizumab
  Q3W,Intravenous Drip
• Drug Carboplatin
  Q3W,Intravenous Drip
• Drug Niraparib
  QD,Oral Administration
• Drug Lenvatinib
  QD,Oral Administration

Primary outcome measures

• Incidence of adverse events (AEs) [Time frame: 60 weeks]
• Incidence of dose-limitingtoxicity (DLT) [Time frame: 60 weeks]
• Incidence of serious adverse event (SAE) [Time frame: 60 weeks]
• Temperatures [Time frame: 60 weeks]
• Pulse in BPM(Beat per Minute) [Time frame: 60 weeks]
• Blood Pressure in mmHg [Time frame: 60 weeks]
• Weight in Kg [Time frame: 60 weeks]
• Height in centimeter [Time frame: 60 weeks]
• Laboratory tests-Blood Routine examination [Time frame: 60 weeks]
• Laboratory tests-Urine Routine test [Time frame: 60 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) 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: 112 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-2417 [Time frame: 112 weeks]
• Biomarker correlation(NaPi2b) [Time frame: 112 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 18-80 years old (including boundary values) , 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, or currently lack or are intolerant of, standard therapy.
• Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing.
• At least one evaluable lesion.
• Subjects must show appropriate organ and marrow function inlaboratory 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.

Single-agent dose of 6mg/kg, 12mg/kg and and combined cohort：Subjects tested positive for biomarkers.

Exclusion criteria

• Previously received with same target therapy.
• Subjects has participated in any other interventional clinical trial within 28 days prior to the first dosing of LM-2417.
• Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-2417, 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.
• Subject who have uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Subjects with known hypersensitivity to antibody therapy;
• Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) for more than 7 days or other systemic immunosuppressive medications within 2 weeks prior to the first dosing of LM-2417.
• Previous or current known autoimmune disease.
• 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 vaccine or live attenuated vaccines within 28 days prior to the first dosing of LM-2417.;
• Subjects who are using therapeutic doses of anticoagulants such as heparin or vitamin K antagonists.
• Subjects who received major surgery or interventional treatment within28 days prior to the first dosing of LM-2417.
• Subject who have history of severe cardiovascular disease.
• Subjects who have uncontrolled or severe illness.
• HIV infection, active HBV or HCV infection.
• 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

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• FuDan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06682780 · LM2417-01-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗