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

Phase 1

Not yet recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: LM-2417; Drug: Docetaxel; Drug: Toripalimab/Tirelizumab; Drug: Carboplatin; Drug: Niraparib; Drug: Lenvatinib

• Registration Number: NCT06682780
• Lead Sponsor: LaNova Medicines Limited

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-11-07
• Study First Submitted QC: 2024-11-07
• Last Update Submitted: 2024-11-07
• Study First Posted: 2024-11-11
• Last Update Posted: 2024-11-11
• Study Start: 2024-12-05
• Primary Completion: 2027-12-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 320

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LM-2417 combination therapy exploratory	Docetaxel	-
LM-2417 combination therapy exploratory	Toripalimab/Tirelizumab	-
LM-2417 combination therapy exploratory	Carboplatin	-
LM-2417 combination therapy exploratory	Niraparib	-
LM-2417 combination therapy exploratory	Lenvatinib	-
LM-2417 combination expansion	LM-2417	-
LM-2417 combination expansion	Docetaxel	-
LM-2417 combination expansion	Toripalimab/Tirelizumab	-
LM-2417 combination expansion	Carboplatin	-
LM-2417 combination expansion	Niraparib	-
LM-2417 combination expansion	Lenvatinib	-
LM2417 Dose Escalation(Q2W/Q3W)	LM-2417	-
LM-2417 combination therapy exploratory	LM-2417	-

Primary Outcome Measures

Name	Time	Method
Pulse in BPM(Beat per Minute)	60 weeks	Phase I/II
Blood Pressure in mmHg	60 weeks	Phase I/II
Weight in Kg	60 weeks	Phase I/II
Height in centimeter	60 weeks	Phase I/II
Laboratory tests-Blood Routine examination	60 weeks	Phase I/II
Laboratory tests-Urine Routine test	60 weeks	Phase I/II
Laboratory tests-Blood biochemistry	60 weeks	Phase I/II
Laboratory tests- Coangulation function	60 weeks	Phase I/II
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	60 weeks	Phase I/II
Incidence of adverse events (AEs)	60 weeks	Phase I/II
Incidence of dose-limitingtoxicity (DLT)	60 weeks	Phase I/II
Incidence of serious adverse event (SAE)	60 weeks	Phase I/II
Temperatures	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in HR	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in RR	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in PR	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in QRS	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in QT	60 weeks	Phase I/II
12-lead electrocardiogram (ECG) in QTcF	60 weeks	Phase I/II
ECOG(Eastern Cooperative Oncology Group) score	60 weeks	Phase I/II
Overall Response Rate (ORR)	76 weeks	Phase I/II

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)	112 weeks	Phase I/II
PK Parameter:Time of Maximum Observed Concentration (Tmax)	112 weeks	Phase I/II
PK Parameter: Area Under the Concentration-time Curve(AUC)	112 weeks	Phase I/II
PK Parameter: Steady State Maximum Concentration(Cmax,ss) PK Parameter: Steady State Maximum Concentration(Cmax,ss)	112 weeks	Phase I/II
PK Parameter: Steady State Minimum Concentration(Cmin,ss)	112 weeks	Phase I/II
PK Parameter: Systemic Clearance at Steady State (CLss)	112 weeks	Phase I/II
PK Parameter: Accumulation Ratio (Rac)	112 weeks	Phase I/II
PK Parameter: Elimination Half-life (t1/2)	112 weeks	Phase I/II
PK Parameter: Volume of Distribution at Steady-State (Vss)	112 weeks	Phase I/II
PK Parameter: Degree of Fluctuation (DF)	112 weeks	Phase I/II
Immunogenicity of LM-2417	112 weeks	Phase I/II
Biomarker correlation(NaPi2b)	112 weeks	Phase I/II
Duration of Response (DOR) in Month	64 weeks	Phase I/II
Disease control rate (DCR) in percentage	64 weeks	Phase I/II
progression-free survival (PFS) in Month	64 weeks	Phase I/II
Safety: AE/SAE (Number of participants with treatment-related adverse events as Overall survival (OS) in Month	64 weeks	Phase I/II
Changes of target lesions from baseline in Millimeter	64 weeks	Phase I/II
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)	64 weeks	Phase I/II

Trial Locations

Locations (1)

FuDan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China