Clinical trial NCT06187402: A Study of LM-24C5 For Advanced Solid Tumors
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-24C5 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: LaNova Medicines Limited
Sponsor class: INDUSTRY
First posted: 2024-01-02
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and tolerability, obtain the recommended phase 2 dose (RP2D)/optimal biologic dose (OBD) and/or Maximum Tolerated Dose (MTD) for LM-24C5 in subjects with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Subjects who are fully informed of the purpose, nature, method and possible adverse reactions of the study, and are willing to participate in the study and sign the informed consent form (ICF) prior to any study related procedures.
2. Aged ≥18 years old when sign the ICF, male or female.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no deterioration within 2 weeks prior to the first dose.
4. Life expectancy ≥ 3 months.
5. Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and have progressed on standard therapy, or are intolerable for available standard therapy, or there is no available standard therapy.
6. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples meet the minimum requirements.
7. At least one measurable lesion according to RECIST v1.1.
8. Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose.
9. Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

Exclusion Criteria:

1. Participate in any other clinical trial within 28 days prior to 1st dosing of LM-24C5.
2. Any prior treatments towards the investigational target.
3. Subjects with anti-tumor treatment within 21 days prior to 1st dosing of LM-24C5, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. the following treatments have different time limits.
4. Any adverse event from prior anti-tumor therapy has not yet recovered to≤ grade 1 of CTCAE v5.0.
5. Subjects with uncontrolled pain.
6. Subjects with known central nervous system (CNS) or meningeal metastasis.
7. Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
8. Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains any monoclonal antibody.
9. 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-24C5.
10. Subjects with the known history of autoimmune disease.
11. Subjects with the history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
12. Use of any live attenuated vaccines within 28 days prior to 1st dosing of LM-24C5.
13. Subjects who are taking therapeutic doses of anticoagulants such as heparin or vitamin K antagonists for presence of active thromboembolic disease.
14. Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-24C5.
15. Subjects who have severe cardiovascular disease.
16. Subjects who have uncontrolled or severe illness, including but not limited to ongoing or active infection
17. Subjects who have a history of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, or organ transplantation, or allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
18. HIV infection, active infection including tuberculosis, HBV and HCV infection, with the exception:
19. Subjects who have other active malignancies which are likely to require the treatment.
20. Child-bearing potential female who have positive results in pregnancy test or are lactating.
21. Subjects who have psychiatric illness or disorders that may preclude study compliance.
22. Subject who is judged as not eligible to participate in this study by the investigator.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 60 weeks
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: 60 weeks
measure: Incidence of serious adverse event (SAE)
timeFrame: 60 weeks
measure: Ear Temperature
timeFrame: 60 weeks
measure: Pulse in BPM(Beat per Minute)
timeFrame: 60 weeks
measure: Blood Pressure in mmHg (Both Systolic and Diastolic blood pressure)
timeFrame: 60 weeks
measure: Number of participants with abnormal Hematology test results
timeFrame: 60 weeks
measure: Number of participants with abnormal Urinalysis test results
timeFrame: 60 weeks
measure: Number of participants with abnormal Blood Biochemistry test results
timeFrame: 60 weeks
measure: Number of participants with abnormal Coagulation test results in PT(Prothrombin time), APTT(Activated partial thromboplastin time), FIB(Fibrinogen), TT(Thrombin time) and INR(International normalized ratio).
timeFrame: 60 weeks
measure: Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc.
timeFrame: 60 weeks
measure: ECOG(Eastern Cooperative Oncology Group) score
timeFrame: 60 weeks
measure: Overall Response Rate (ORR)
timeFrame: 36 weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
timeFrame: 96 weeks
measure: PK Parameter:Time of Maximum Observed Concentration (Tmax)
timeFrame: 96 weeks
measure: PK Parameter: Area Under the Concentration-time Curve(AUC)
timeFrame: 96 weeks
measure: PK Parameter: Steady State Maximum Concentration(Cmax,ss)
timeFrame: 96 weeks
measure: PK Parameter: Steady State Minimum Concentration(Cmin,ss)
timeFrame: 96 weeks
measure: PK Parameter: Systemic Clearance at Steady State (CLss)
timeFrame: 96 weeks
measure: PK Parameter: Accumulation Ratio (Rac)
timeFrame: 96 weeks
measure: PK Parameter: Elimination Half-life (t1/2)
timeFrame: 96 weeks
measure: PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: 96 weeks
measure: PK Parameter: Degree of Fluctuation (DF)
timeFrame: 96 weeks
measure: Immunogenicity of LM-24C5
timeFrame: 96 weeks
measure: Duration of Response (DOR) in Month
timeFrame: 96 weeks
measure: Disease control rate (DCR) in percentage
timeFrame: 96 weeks
measure: progression-free survival (PFS) in Month
timeFrame: 96 weeks
measure: Overall survival (OS) in Month
timeFrame: 60 weeks
measure: Changes of target lesions from baseline in Millimeter.
timeFrame: 96 weeks
measure: Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)
timeFrame: 36 weeks
measure: Ear Temperature
timeFrame: 36 weeks
measure: Pulse in BPM (Beat per Minute)
timeFrame: 36 weeks
measure: Blood Pressure in mmHg (Both Systolic and Diastolic blood pressure)
timeFrame: 36 weeks
measure: Number of participants with abnormal Hematology test results
timeFrame: 36 weeks
measure: Number of participants with abnormal Urinalysis test results
timeFrame: 36 weeks
measure: Number of participants with abnormal Blood Biochemistry test results
timeFrame: 36 weeks
measure: Number of participants with abnormal Coagulation test results in PT(Prothrombin time), APTT(Activated partial thromboplastin time), FIB(Fibrinogen), TT(Thrombin time) and INR(International normalized ratio).
timeFrame: 36 weeks
measure: 12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc.
timeFrame: 36 weeks
measure: ECOG(Eastern Cooperative Oncology Group) score
timeFrame: 36 weeks
Other outcomes:
measure: Relationship between the biomarkers and the anti-tumor activity
timeFrame: 96 weeks
Locations:
city: Los Angeles
country: United States
facility: University of Southern California (USC) - Norris Comprehensive Cancer Center
state: California
city: Ocala
country: United States
facility: Ocala Oncology
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Melvan and Bren Simon Cancer Center
state: Indiana
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, P.C.
state: Virginia
Study officials:
affiliation: LaNova
name: Terry Pang
role: STUDY_DIRECTOR
References: