A Phase I/II Study of LM-101 Injection in Patients With Advanced Malignant Tumors
- Registration Number
- NCT05615974
- Lead Sponsor
- LaNova Medicines Limited
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 139
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LM101 Dose Escalation LM101 - LM101 combination therapy exploratory LM101 - LM101 combination therapy exploratory Toripalimab - LM101 combination therapy exploratory Rituximab - LM101 combination expansion LM101 - LM101 combination expansion Toripalimab - LM101 combination expansion Rituximab -
- Primary Outcome Measures
Name Time Method Incidence of adverse events (AEs) 48 weeks Phase 1
Incidence of dose-limitingtoxicity (DLT) 48 weeks Phase 1
Incidence of serious adverse event (SAE) 48 weeks Phase 1
Temperature in ℃ 48 weeks Phase 1
Pulse in BPM(Beat per Minute) 48 weeks Phase 1
Blood Pressure in mmHg 48 weeks Phase 1
Weight in Kg 48 weeks Phase 1
Height in centimeter 48 weeks Phase 1
Laboratory tests-Blood Routine examination 48 weeks Phase 1
Laboratory tests-Urine Routine test 48 weeks Phase 1
Laboratory tests-Blood biochemistry 48 weeks Phase 1
Laboratory tests- Coangulation function 48 weeks Phase 1
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage 48 weeks Phase 1
12-lead electrocardiogram (ECG) in QTcF. 48 weeks Phase 1
12-lead electrocardiogram (ECG) in QT. 48 weeks Phase 1
12-lead electrocardiogram (ECG) in QRS. 48 weeks Phase 1
12-lead electrocardiogram (ECG) in HR. 48 weeks Phase 1
12-lead electrocardiogram (ECG) in RR. 48 weeks Phase 1
12-lead electrocardiogram (ECG) in PR. 48 weeks Phase 1
ECOG(Eastern Cooperative Oncology Group) score 48 weeks Phase 1
Overall Response Rate (ORR) 64 weeks Phase 2
- Secondary Outcome Measures
Name Time Method PK Parameter: Degree of Fluctuation (DF) 112 weeks Phase 1 and 2
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) 112 weeks Phase 1 and 2
PK Parameter:Time of Maximum Observed Concentration (Tmax) 112 weeks Phase 1 and 2
PK Parameter: Area Under the Concentration-time Curve(AUC) 112 weeks Phase 1 and 2
PK Parameter: Steady State Maximum Concentration(Cmax,ss) 112 weeks Phase 1 and 2
PK Parameter: Steady State Minimum Concentration(Cmin,ss) 112 weeks Phase 1 and 2
PK Parameter: Systemic Clearance at Steady State (CLss) 112 weeks Phase 1 and 2
PK Parameter: Accumulation Ratio (Rac) 48 weeks Phase 1 and 2
PK Parameter: Elimination Half-life (t1/2) 112 weeks Phase 1
PK Parameter: Volume of Distribution at Steady-State (Vss) 112 weeks Phase 1 and 2
Immunogenicity of LM-101 112 weeks Phase 1 and 2; Anti-Drug antibody and Nab (if neccessary) will be tested.
Receptor Occupancy of LM-101 48 weeks Phase 1
Biomarker correlation (CD8/CD47/CD68/CD163/PD-L1) 112 weeks Phase 1 and 2
Duration of Response (DOR) in Month 64 weeks Phase 2
Disease control rate (DCR) in percentage 64 weeks Phase 2
progression-free survival (PFS) in Month 64 weeks Phase 2
Overall survival (OS) in Month 64 weeks Phase 2
Changes of target lesions from baseline in Millimeter. 64 weeks Phase 2
Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) 64 weeks Phase 2
Temperature in ℃ 64 weeks Phase 2
Pulse in BPM(Beat per Minute) 64 weeks Phase 2
Blood Pressure in mmHg 64 weeks Phase 2
Weight in Kg 64 weeks Phase 2
Height in centimeter 64 weeks Phase 2
Laboratory tests-Blood Routine examination 64 weeks Phase 2
Laboratory tests-Urine Routine test 64 weeks Phase 2
Laboratory tests-Blood biochemistry 64 weeks Phase 2
Laboratory tests- Coangulation function 64 weeks Phase 2
12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc. 64 weeks Phase 2
ECOG(Eastern Cooperative Oncology Group) score 64 weeks Phase 2
Trial Locations
- Locations (5)
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Linyi Cancer Hospital
🇨🇳Linyi, Shandong, China
Beijing Tongren Hospital, CMU
🇨🇳Beijing, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China