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

Malignant Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05615974
• Other study ID #: LM101-01-103
• Status: Suspended
• Phase: Phase 1/Phase 2
• Start date: January 11, 2023
• Est. completion date: August 2025

Study information

• Verified date: November 2023
• Source: LaNova Medicines Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 145
• Est. completion date: August 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 must show appropriate organ and marrow function in laboratory examinations

within 7 days prior to the first dose:

8. 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.

9. 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 CD47 or SIRPa.

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. Subjects with symptomatic/active central nervous system (CNS) metastases.

6. Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.

7. Subjects with known hypersensitivity to antibody therapy.

8. 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.

9. 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.

10. Subject who has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

11. Use of any live attenuated vaccines within 28 days prior to the first dosing of LM-101.

12. Subjects who received major surgery or interventional treatment within 28 days prior to the first dosing of LM-101 (excluding tumor biopsy, puncture, etc.).

13. Subjects who have uncontrolled or severe illness.

14. Subjects who have a history of immunodeficiency disease.

15. HIV infection, active tuberculosis or active HBV and HCV infection.

16. Subjects who have other active invasive cancers, other than the one treated in this trial, within 5 years prior to screening.

17. Child-bearing potential female who have positive results in pregnancy test or are lactating.

18. Subject who is judged as not eligible to participate in this study by the investigator.

Related Conditions & MeSH terms

• Malignant Tumors
• Neoplasms

Intervention

Drug:
• LM101
Administered intravenously
• Toripalimab
Administered intravenously
• Rituximab
Administered intravenously
• Envafolimab
Administered intravenously

Locations

Country	Name	City	State
China	Beijing Tongren Hospital, CMU	Beijing
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Linyi Cancer Hospital	Linyi	Shandong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
LaNova Medicines Limited

Country where clinical trial is conducted

China, 

Outcome

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