Clinical trial NCT06682780: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: LaNova Medicines Limited
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
2. Aged 18-80 years old (including boundary values) , male or female.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Life expectancy ≥ 3 months.
5. Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, or currently lack or are intolerant of, standard therapy.
6. Subjects must have Archived Samples or fresh tumor tissue specimens are required for testing.
7. At least one evaluable lesion.
8. Subjects must show appropriate organ and marrow function inlaboratory examinations within 7 days prior to the first dose.
9. 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.
10. 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:

1. Previously received with same target therapy.
2. Subjects has participated in any other interventional clinical trial within 28 days prior to the first dosing of LM-2417.
3. Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-2417, including radiotherapy, chemotherapy, endocrine therapy, and immunotherapy, etc.
4. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
5. Poorly controlled tumor-related pain.
6. Subjects with symptomatic/active central nervous system (CNS)metastases.
7. Subject who have uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
8. Subjects with known hypersensitivity to antibody therapy;
9. 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.
10. Previous or current known autoimmune disease.
11. Subject who has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
12. Use of any live vaccine or live attenuated vaccines within 28 days prior to the first dosing of LM-2417.;
13. Subjects who are using therapeutic doses of anticoagulants such as heparin or vitamin K antagonists.
14. Subjects who received major surgery or interventional treatment within28 days prior to the first dosing of LM-2417.
15. Subject who have history of severe cardiovascular disease.
16. Subjects who have uncontrolled or severe illness.
17. HIV infection, active HBV or HCV infection.
18. Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.
19. Child-bearing potential female who have positive results in pregnancy test or are lactating.
20. Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial.
21. 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-limitingtoxicity (DLT)
timeFrame: 60 weeks
measure: Incidence of serious adverse event (SAE)
timeFrame: 60 weeks
measure: Temperatures
timeFrame: 60 weeks
measure: Pulse in BPM(Beat per Minute)
timeFrame: 60 weeks
measure: Blood Pressure in mmHg
timeFrame: 60 weeks
measure: Weight in Kg
timeFrame: 60 weeks
measure: Height in centimeter
timeFrame: 60 weeks
measure: Laboratory tests-Blood Routine examination
timeFrame: 60 weeks
measure: Laboratory tests-Urine Routine test
timeFrame: 60 weeks
measure: Laboratory tests-Blood biochemistry
timeFrame: 60 weeks
measure: Laboratory tests- Coangulation function
timeFrame: 60 weeks
measure: Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in HR
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in RR
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in PR
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in QRS
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in QT
timeFrame: 60 weeks
measure: 12-lead electrocardiogram (ECG) in QTcF
timeFrame: 60 weeks
measure: ECOG(Eastern Cooperative Oncology Group) score
timeFrame: 60 weeks
measure: Overall Response Rate (ORR)
timeFrame: 76 weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
timeFrame: 112 weeks
measure: PK Parameter:Time of Maximum Observed Concentration (Tmax)
timeFrame: 112 weeks
measure: PK Parameter: Area Under the Concentration-time Curve(AUC)
timeFrame: 112 weeks
measure: PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss)
timeFrame: 112 weeks
measure: PK Parameter: Steady State Minimum Concentration(Cmin,ss)
timeFrame: 112 weeks
measure: PK Parameter: Systemic Clearance at Steady State (CLss)
timeFrame: 112 weeks
measure: PK Parameter: Accumulation Ratio (Rac)
timeFrame: 112 weeks
measure: PK Parameter: Elimination Half-life (t1/2)
timeFrame: 112 weeks
measure: PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: 112 weeks
measure: PK Parameter: Degree of Fluctuation (DF)
timeFrame: 112 weeks
measure: Immunogenicity of LM-2417
timeFrame: 112 weeks
measure: Biomarker correlation(NaPi2b)
timeFrame: 112 weeks
measure: Duration of Response (DOR) in Month
timeFrame: 64 weeks
measure: Disease control rate (DCR) in percentage
timeFrame: 64 weeks
measure: progression-free survival (PFS) in Month
timeFrame: 64 weeks
measure: Safety: AE/SAE (Number of participants with treatment-related adverse events as Overall survival (OS) in Month
timeFrame: 64 weeks
measure: Changes of target lesions from baseline in Millimeter
timeFrame: 64 weeks
measure: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0) Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)
timeFrame: 64 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: FuDan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: