Clinical trial NCT05615974: A Phase I/II Study of LM-101 Injection in Patients With Advanced Malignant Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Malignant Tumors
Lead sponsor: LaNova Medicines Limited
Sponsor class: INDUSTRY
First posted: 2022-11-14
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


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. 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.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 48 weeks
measure: Incidence of dose-limitingtoxicity (DLT)
timeFrame: 48 weeks
measure: Incidence of serious adverse event (SAE)
timeFrame: 48 weeks
measure: Temperature in ℃
timeFrame: 48 weeks
measure: Pulse in BPM(Beat per Minute)
timeFrame: 48 weeks
measure: Blood Pressure in mmHg
timeFrame: 48 weeks
measure: Weight in Kg
timeFrame: 48 weeks
measure: Height in centimeter
timeFrame: 48 weeks
measure: Laboratory tests-Blood Routine examination
timeFrame: 48 weeks
measure: Laboratory tests-Urine Routine test
timeFrame: 48 weeks
measure: Laboratory tests-Blood biochemistry
timeFrame: 48 weeks
measure: Laboratory tests- Coangulation function
timeFrame: 48 weeks
measure: Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in QTcF.
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in QT.
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in QRS.
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in HR.
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in RR.
timeFrame: 48 weeks
measure: 12-lead electrocardiogram (ECG) in PR.
timeFrame: 48 weeks
measure: ECOG(Eastern Cooperative Oncology Group) score
timeFrame: 48 weeks
measure: Overall Response Rate (ORR)
timeFrame: 64 weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
timeFrame: 112 weeks
measure: PK Parameter:Time of Maximum Observed Concentration (Tmax)
timeFrame: 112 weeks
measure: PK Parameter: Area Under the Concentration-time Curve(AUC)
timeFrame: 112 weeks
measure: PK Parameter: Steady State Maximum Concentration(Cmax,ss)
timeFrame: 112 weeks
measure: PK Parameter: Steady State Minimum Concentration(Cmin,ss)
timeFrame: 112 weeks
measure: PK Parameter: Systemic Clearance at Steady State (CLss)
timeFrame: 112 weeks
measure: PK Parameter: Accumulation Ratio (Rac)
timeFrame: 48 weeks
measure: PK Parameter: Elimination Half-life (t1/2)
timeFrame: 112 weeks
measure: PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: 112 weeks
measure: PK Parameter: Degree of Fluctuation (DF)
timeFrame: 112 weeks
measure: Immunogenicity of LM-101
timeFrame: 112 weeks
measure: Receptor Occupancy of LM-101
timeFrame: 48 weeks
measure: Biomarker correlation (CD8/CD47/CD68/CD163/PD-L1)
timeFrame: 112 weeks
measure: Duration of Response (DOR) in Month
timeFrame: 64 weeks
measure: Disease control rate (DCR) in percentage
timeFrame: 64 weeks
measure: progression-free survival (PFS) in Month
timeFrame: 64 weeks
measure: Overall survival (OS) in Month
timeFrame: 64 weeks
measure: Changes of target lesions from baseline in Millimeter.
timeFrame: 64 weeks
measure: Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)
timeFrame: 64 weeks
measure: Temperature in ℃
timeFrame: 64 weeks
measure: Pulse in BPM(Beat per Minute)
timeFrame: 64 weeks
measure: Blood Pressure in mmHg
timeFrame: 64 weeks
measure: Weight in Kg
timeFrame: 64 weeks
measure: Height in centimeter
timeFrame: 64 weeks
measure: Laboratory tests-Blood Routine examination
timeFrame: 64 weeks
measure: Laboratory tests-Urine Routine test
timeFrame: 64 weeks
measure: Laboratory tests-Blood biochemistry
timeFrame: 64 weeks
measure: Laboratory tests- Coangulation function
timeFrame: 64 weeks
measure: 12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc.
timeFrame: 64 weeks
measure: ECOG(Eastern Cooperative Oncology Group) score
timeFrame: 64 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Beijing
country: China
facility: Beijing Tongren Hospital, CMU
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
References: