Study of LM-299 in Subjects Advanced Malignant Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Tumors
• Intervention / Treatment: Drug: LM-299

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alex Yuan; Phone Number: +8615901815211; Email: alexyuan@lanovamed.com

Study Locations

• Australia
  • West Australia
    • Perth, West Australia, Australia
      • Not yet recruiting
      • One Clinical Research
      • Contact: Dr Mihitha Ariyapperuma
• China
  • Henan
    • Xinxiang, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xinxiang Medical University
      • Contact: Weizheng Kou
  • Shandong
    • Liaocheng, Shandong, China
      • Not yet recruiting
      • Liaocheng People's Hospital
      • Contact: Baozhong Wang
    • Zibo, Shandong, China
      • Not yet recruiting
      • Zibo Municipal Hospital
      • Contact: Rusen Zhao
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Shanghai Dongfang Hospital (Tongji University Affiliated Dongfang Hospital)
      • Contact: Junli Xue
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Gobroad Cancer Hospital China Pharmaceutical University
      • Contact: Jin Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM-299 Dose Escalation at different dose levels	Drug: LM-299; Q2W/Q3W,Intravenous Drip
Experimental: LM-299 Dose Escalation Backfill Cohorts	Drug: LM-299; Q2W/Q3W,Intravenous Drip

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limitingtoxicity (DLT)	Phase 1	53 weeks
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	Phase 1	53 weeks
Overall Response Rate (ORR)	Phase 2	50 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Phase 1	53 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Parameter: Area Under the Concentration-time Curve(AUClast)	Phase 1 and 2	103 weeks
PK Parameter: Area Under the Concentration-time Curve(AUCtau)	Phase 1 and 2	103 weeks
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)	Phase 1 and 2	103 weeks
PK Parameter:Time of Maximum Observed Concentration (Tmax)	Phase 1 and 2	103 weeks
PK Parameter: Elimination Half-life (t1/2)	Phase 1 and 2	103 weeks
PK Parameter: Steady State Maximum Concentration(Cmax,ss)	Phase 1 and 2	103 weeks
PK Parameter: Steady State Minimum Concentration(Cmin,ss)	Phase 1 and 2	103 weeks
PK Parameter: Systemic Clearance at Steady State (CLss)	Phase 1 and 2	103 weeks
PK Parameter: Volume of Distribution at Steady-State (Vss)	Phase 1 and 2	103 weeks
PK Parameter: Accumulation Ratio (Rac AUC)	Phase 1 and 2	103 weeks
PK Parameter: Degree of Fluctuation (DF)	Phase 1 and 2	103 weeks
Overall Response Rate (ORR)	Phase 1	53 weeks
Duration of Response (DOR) in Month	Phase 1 and 2	103 weeks
Disease control rate (DCR) in percentage	Phase 1 and 2	103 weeks
progression-free survival (PFS) in Month	Phase 1 and 2	103 weeks
Overall survival (OS) in Month	Phase 1 and 2	103 weeks
PK Parameter: Accumulation Ratio (Rac Cmax)	Phase 1 and 2	103 weeks

Collaborators and Investigators

• Sponsor: LaNova Medicines Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 21, 2024

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LM299-01-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No