A Phase I/II Study of LM-101 Injection in Patients With Advanced Malignant Tumors

A Phase I/II, Open-label, Dose Escalation, and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of LM-101 Injection as a Single Agent or Combination Therapy in Patients With Advanced Malignant Tumors

This study is to assess the safety and tolerability, obtain Maximum Tolerated Dose (MTD) and/or the recommended phase 2 dose (RP2D) of LM-101 as a single agent or in combination in patients with advanced malignant tumors

Study Overview

• Status: Recruiting
• Conditions: Malignant Tumors
• Intervention / Treatment: Drug: Rituximab; Drug: LM101; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 139
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• China
  • Beijing, China
    • Terminated
    • Beijing Tongren Hospital, CMU
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Dongmei Ji
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yi Xia
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: fuling Zhou
  • Shandong
    • Linyi, Shandong, China
      • Not yet recruiting
      • Linyi Cancer Hospital
      • Contact: Jianhua Shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (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. Aged ≥18 years old, 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, and have progressed on standard therapy.
6. At least one evaluable lesion.
7. Subjects in the combination therapy group must have Archived Samples or fresh tumor tissue specimens are required for testing.
8. Subjects must show appropriate organ and marrow function in laboratory 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.

Exclusion Criteria:

1. Subject has received prior investigational therapy directed at the same target therapy.
2. Subjects has participated in any other interventional clinical trial within 21 days prior to the first dosing of LM-101.
3. Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-101, 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. Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
8. Subjects with known hypersensitivity to antibody therapy.
9. Subjects who take systemic corticosteroids (> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medicationswithin 2 weeks prior to the first dosing of LM-101.
10. Subjects with the known history of autoimmune disease with the exception of subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone.
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 attenuated vaccines within 28 days prior to the first dosing of LM-101.
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 within 28 days prior to the first dosing of LM-101 (excluding tumor biopsy, puncture, etc.).
15. Subjects who have history of severe cardiovascular disease.
16. Subjects who have uncontrolled or severe illness.
17. Subjects who have a history of immunodeficiency disease.
18. HIV infection, active tuberculosis or active HBV and HCV infection.
19. Subjects who have Known history of active tuberculosis.
20. Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.
21. Child-bearing potential female who have positive results in pregnancy test or are lactating.
22. Subject who have a known psychiatric diseases or disorders that may affect compliance with the trial.
23. 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: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM101 Dose Escalation	Drug: LM101; Administered intravenously
Experimental: LM101 combination therapy exploratory	Drug: Rituximab; Administered intravenously; Drug: LM101; Administered intravenously; Drug: Toripalimab; Administered intravenously
Experimental: LM101 combination expansion	Drug: Rituximab; Administered intravenously; Drug: LM101; Administered intravenously; Drug: Toripalimab; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	Phase 1	48 weeks
Incidence of dose-limitingtoxicity (DLT)	Phase 1	48 weeks
Incidence of serious adverse event (SAE)	Phase 1	48 weeks
Temperature in ℃	Phase 1	48 weeks
Pulse in BPM(Beat per Minute)	Phase 1	48 weeks
Blood Pressure in mmHg	Phase 1	48 weeks
Weight in Kg	Phase 1	48 weeks
Height in centimeter	Phase 1	48 weeks
Laboratory tests-Blood Routine examination	Phase 1	48 weeks
Laboratory tests-Urine Routine test	Phase 1	48 weeks
Laboratory tests-Blood biochemistry	Phase 1	48 weeks
Laboratory tests- Coangulation function	Phase 1	48 weeks
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage	Phase 1	48 weeks
ECOG(Eastern Cooperative Oncology Group) score	Phase 1	48 weeks
Overall Response Rate (ORR)	Phase 2	64 weeks
12-lead electrocardiogram (ECG) in QTcF.	Phase 1	48 weeks
12-lead electrocardiogram (ECG) in QT.	Phase 1	48 weeks
12-lead electrocardiogram (ECG) in QRS.	Phase 1	48 weeks
12-lead electrocardiogram (ECG) in HR.	Phase 1	48 weeks
12-lead electrocardiogram (ECG) in RR.	Phase 1	48 weeks
12-lead electrocardiogram (ECG) in PR.	Phase 1	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)	Phase 1 and 2	112 weeks
PK Parameter:Time of Maximum Observed Concentration (Tmax)	Phase 1 and 2	112 weeks
PK Parameter: Area Under the Concentration-time Curve(AUC)	Phase 1 and 2	112 weeks
PK Parameter: Steady State Maximum Concentration(Cmax,ss)	Phase 1 and 2	112 weeks
PK Parameter: Steady State Minimum Concentration(Cmin,ss)	Phase 1 and 2	112 weeks
PK Parameter: Systemic Clearance at Steady State (CLss)	Phase 1 and 2	112 weeks
PK Parameter: Accumulation Ratio (Rac)	Phase 1 and 2	48 weeks
PK Parameter: Elimination Half-life (t1/2)	Phase 1	112 weeks
PK Parameter: Volume of Distribution at Steady-State (Vss)	Phase 1 and 2	112 weeks
PK Parameter: Degree of Fluctuation (DF)	Phase 1 and 2	112 weeks
Immunogenicity of LM-101	Phase 1 and 2; Anti-Drug antibody and Nab (if neccessary) will be tested.	112 weeks
Receptor Occupancy of LM-101	Phase 1	48 weeks
Biomarker correlation (CD8/CD47/CD68/CD163/PD-L1)	Phase 1 and 2	112 weeks
Duration of Response (DOR) in Month	Phase 2	64 weeks
Disease control rate (DCR) in percentage	Phase 2	64 weeks
progression-free survival (PFS) in Month	Phase 2	64 weeks
Overall survival (OS) in Month	Phase 2	64 weeks
Changes of target lesions from baseline in Millimeter.	Phase 2	64 weeks
Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)	Phase 2	64 weeks
Temperature in ℃	Phase 2	64 weeks
Pulse in BPM(Beat per Minute)	Phase 2	64 weeks
Blood Pressure in mmHg	Phase 2	64 weeks
Weight in Kg	Phase 2	64 weeks
Height in centimeter	Phase 2	64 weeks
Laboratory tests-Blood Routine examination	Phase 2	64 weeks
Laboratory tests-Urine Routine test	Phase 2	64 weeks
Laboratory tests-Blood biochemistry	Phase 2	64 weeks
Laboratory tests- Coangulation function	Phase 2	64 weeks
12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc.	Phase 2	64 weeks
ECOG(Eastern Cooperative Oncology Group) score	Phase 2	64 weeks

Collaborators and Investigators

• Sponsor: LaNova Medicines Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2023
• Primary Completion (Estimated): January 11, 2027
• Study Completion (Estimated): January 11, 2028

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: November 8, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Rituximab
• Other Study ID Numbers: LM101-01-103

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