Clinical trial NCT06650566: Study of LM-299 in Subjects Advanced Malignant Tumors
Official title: A Phase I/II, Open-label, Dose Escalation and Dose Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of LM-299 Injection as Monotherapy or in Combination With Other Anti-tumor Therapies in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Tumors
Lead sponsor: LaNova Medicines Limited
Sponsor class: INDUSTRY
First posted: 2024-10-21
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For Phase I Dose Escalation Stage, to assess the safety and tolerability of LM-299 in patients with advanced solid tumors,determine the maximum tolerated dose (MTD) or optimal biological dose (OBD), and explorethe recommended dose for expansion (RDE) in patients with advanced solid tumours..

For Phase II Dose Expansion Stage, to assess the antitumor activity of LM-299 in patients with various advanced solid tumors.


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. Participant must be 18- 18 years or the legal age of consent at the time of signing the ICF.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Life expectancy ≥ 3 months.
5. Patients with advanced solid tumors confirmed by histopathological diagnosis who have failed standard treatment, are intolerant to standard treatment, or for whom standard treatment is currently unsuitable.
6. Pre-treatment archived tumour tissue (within 5 years) or fresh samples could be provided for biomarker analysis.
7. Must have at least one measurable lesion according to RECIST v1.1.
8. Adequate organ and bone marrow function as defined by protocol.
9. Female subjects of childbearing potential or male subjects with partners of childbearing potential agree to use highly effective contraception.
10. 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-299.
2. Subjects who have received the anti-tumor treatments within the specified time periods prior to the first dosing of LM-299.
3. Any adverse event from prior anti-tumour therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
4. Subjects with uncontrolled tumour-related pain.
5. Subjects with known central nervous system (CNS) or meningeal metastasis.
6. Qualitative urine protein results ≥ 3+.
7. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to 1st dosing of LM-299.
8. Any life-threatening bleeding event that occurred within 3 months prior to 1st dosing of LM-299.
9. Subjects with esophageal or gastric varices requiring immediate intervention or a history of variceal bleeding .
10. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or more severe liver cirrhosis.
11. Subjects who have clinically uncontrollable third-space fluid accumulatio.
12. Radiographic evidence of tumor invading surrounding vital organs or the risk of esophagotracheal fistula or esophagopleural fistula, tumor surrounding or invading the major blood vessels, or presence of intratumoral cavity formation.
13. History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of the study drug.
14. Patients with complete or incomplete intestinal obstruction within 3 months prior to the first dose of the study drug or patientswho are currently at the risk of intestinal perforation.
15. Subjects who are known to be allergic to antibody treatment.
16. Subjects who take systemic corticosteroids (≥ 10 mg/day of prednisone or equivalent) for more than 7 days within 2 weeks prior to the first dose of LM-299.
17. Subjects with the known history of autoimmune disease.
18. Patients with a history of active or previously confirmed inflammatory bowel disease.
19. Patients with a history of or currently having interstitial pneumonia requiring systemic corticosteroid treatment.
20. Received live vaccines or attenuated live vaccines within 28 days prior to the first dose of the study drug.
21. Currently using anticoagulants such as therapeutic doses of heparin or vitamin K antagonists.
22. Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-299 (excluding tumour biopsy, puncture, etc.).
23. Subjects who have severe cardiovascular and and cerebrovascular diseases.
24. Patients with severe infections within 4 weeks prior to the first dose.
25. Patients with a history of immunodeficiency.
26. Individuals with HIV infection, active HBV or HCV infection .
27. Patients with known active tuberculosis (TB). Suspected active TB should be ruled out through clinical examination.
28. Patients who have had other malignancies within 5 years prior to the first dose of the study drug.
29. Women of childbearing age who test positive for pregnancy within 7 days prior to the first dose of the study drug or are breastfeeding.
30. Individuals with known psychiatric disorders or illnesses that may affect adherence to the trial.
31. Patients with local or systemic diseases caused by non-malignant tumors.
32. Subject who is judged as not eligible to participate in this study by the investigator.

Primary outcomes:
measure: Incidence of dose-limitingtoxicity (DLT)
timeFrame: 53 weeks
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 53 weeks
measure: Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
timeFrame: 53 weeks
measure: Overall Response Rate (ORR)
timeFrame: 50 weeks
Secondary outcomes:
measure: PK Parameter: Area Under the Concentration-time Curve(AUClast)
timeFrame: 103 weeks
measure: PK Parameter: Area Under the Concentration-time Curve(AUCtau)
timeFrame: 103 weeks
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
timeFrame: 103 weeks
measure: PK Parameter:Time of Maximum Observed Concentration (Tmax)
timeFrame: 103 weeks
measure: PK Parameter: Elimination Half-life (t1/2)
timeFrame: 103 weeks
measure: PK Parameter: Steady State Maximum Concentration(Cmax,ss)
timeFrame: 103 weeks
measure: PK Parameter: Steady State Minimum Concentration(Cmin,ss)
timeFrame: 103 weeks
measure: PK Parameter: Systemic Clearance at Steady State (CLss)
timeFrame: 103 weeks
measure: PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: 103 weeks
measure: PK Parameter: Accumulation Ratio (Rac AUC)
timeFrame: 103 weeks
measure: PK Parameter: Degree of Fluctuation (DF)
timeFrame: 103 weeks
measure: Overall Response Rate (ORR)
timeFrame: 53 weeks
measure: Duration of Response (DOR) in Month
timeFrame: 103 weeks
measure: Disease control rate (DCR) in percentage
timeFrame: 103 weeks
measure: progression-free survival (PFS) in Month
timeFrame: 103 weeks
measure: Overall survival (OS) in Month
timeFrame: 103 weeks
measure: PK Parameter: Accumulation Ratio (Rac Cmax)
timeFrame: 103 weeks
Other outcomes:
Locations:
city: Perth
country: Australia
facility: One Clinical Research
state: West Australia
city: Xinxiang
country: China
facility: the first affiliated hospital of Xinxiang medical University
state: Henan
city: Liaocheng
country: China
facility: Liaocheng people's hospital
state: Shandong
city: Zibo
country: China
facility: Zibo municipal hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Dongfang Hospital (Tongji University Affiliated Dongfang Hospital)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai GoBroad Cancer Hospital China Pharmaceutical University
state: Shanghai
Study officials:
References: