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
Overview
- Phase
- Phase 1
- Intervention
- Toripalimab
- Conditions
- Malignant Tumors
- Sponsor
- LaNova Medicines Limited
- Enrollment
- 139
- Locations
- 5
- Primary Endpoint
- Incidence of dose-limitingtoxicity (DLT)
- Status
- Recruiting
- Last Updated
- last year
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who are willing to participate in the study and sign the informed consent form (ICF) prior to any procedure.
- •Aged ≥18 years old, male or female.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy ≥ 3 months.
- •Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and have progressed on standard therapy.
- •At least one evaluable lesion.
- •Subjects in the combination therapy group must have Archived Samples or fresh tumor tissue specimens are required for testing.
- •Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose:
- •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.
- •Subjects who can communicate well with investigators and understand and adhere to the requirements of this study.
Exclusion Criteria
- •Subject has received prior investigational therapy directed at the same target therapy.
- •Subjects has participated in any other interventional clinical trial within 21 days prior to the first dosing of LM-
- •Subjects with anti-tumor treatment within 21 days prior to the first dosing of LM-101, including radiotherapy, chemotherapy, endocrine therapy, and immunotherapy, etc.
- •Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.
- •Poorly controlled tumor-related pain.
- •Subjects with symptomatic/active central nervous system (CNS) metastases.
- •Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
- •Subjects with known hypersensitivity to antibody therapy.
- •Subjects who take systemic corticosteroids (\> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medicationswithin 2 weeks prior to the first dosing of LM-
- •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.
Arms & Interventions
LM101 combination therapy exploratory
Intervention: Toripalimab
LM101 combination therapy exploratory
Intervention: Rituximab
LM101 combination expansion
Intervention: LM101
LM101 combination expansion
Intervention: Toripalimab
LM101 combination expansion
Intervention: Rituximab
LM101 Dose Escalation
Intervention: LM101
LM101 combination therapy exploratory
Intervention: LM101
Outcomes
Primary Outcomes
Incidence of dose-limitingtoxicity (DLT)
Time Frame: 48 weeks
Phase 1
Incidence of adverse events (AEs)
Time Frame: 48 weeks
Phase 1
Incidence of serious adverse event (SAE)
Time Frame: 48 weeks
Phase 1
Temperature in ℃
Time Frame: 48 weeks
Phase 1
Pulse in BPM(Beat per Minute)
Time Frame: 48 weeks
Phase 1
Blood Pressure in mmHg
Time Frame: 48 weeks
Phase 1
Weight in Kg
Time Frame: 48 weeks
Phase 1
Height in centimeter
Time Frame: 48 weeks
Phase 1
Laboratory tests-Blood Routine examination
Time Frame: 48 weeks
Phase 1
Laboratory tests-Urine Routine test
Time Frame: 48 weeks
Phase 1
Laboratory tests-Blood biochemistry
Time Frame: 48 weeks
Phase 1
Laboratory tests- Coangulation function
Time Frame: 48 weeks
Phase 1
Echocardiography- LVEF(Left Ventricular Ejection Fraction) in percentage
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in QTcF.
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in QT.
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in QRS.
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in HR.
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in RR.
Time Frame: 48 weeks
Phase 1
12-lead electrocardiogram (ECG) in PR.
Time Frame: 48 weeks
Phase 1
ECOG(Eastern Cooperative Oncology Group) score
Time Frame: 48 weeks
Phase 1
Overall Response Rate (ORR)
Time Frame: 64 weeks
Phase 2
Secondary Outcomes
- Laboratory tests-Blood biochemistry(64 weeks)
- Laboratory tests- Coangulation function(64 weeks)
- 12-lead electrocardiogram (ECG) in RR, PR, QRS, QT, QTcF etc.(64 weeks)
- ECOG(Eastern Cooperative Oncology Group) score(64 weeks)
- Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)(112 weeks)
- PK Parameter:Time of Maximum Observed Concentration (Tmax)(112 weeks)
- PK Parameter: Area Under the Concentration-time Curve(AUC)(112 weeks)
- PK Parameter: Steady State Maximum Concentration(Cmax,ss)(112 weeks)
- PK Parameter: Steady State Minimum Concentration(Cmin,ss)(112 weeks)
- PK Parameter: Systemic Clearance at Steady State (CLss)(112 weeks)
- PK Parameter: Accumulation Ratio (Rac)(48 weeks)
- PK Parameter: Elimination Half-life (t1/2)(112 weeks)
- PK Parameter: Volume of Distribution at Steady-State (Vss)(112 weeks)
- PK Parameter: Degree of Fluctuation (DF)(112 weeks)
- Immunogenicity of LM-101(112 weeks)
- Receptor Occupancy of LM-101(48 weeks)
- Biomarker correlation (CD8/CD47/CD68/CD163/PD-L1)(112 weeks)
- Duration of Response (DOR) in Month(64 weeks)
- Disease control rate (DCR) in percentage(64 weeks)
- progression-free survival (PFS) in Month(64 weeks)
- Overall survival (OS) in Month(64 weeks)
- Changes of target lesions from baseline in Millimeter.(64 weeks)
- Safety: AE/SAE (Number of participants with treatment-related adverse events as assessed by CTCAE v5.0)(64 weeks)
- Temperature in ℃(64 weeks)
- Pulse in BPM(Beat per Minute)(64 weeks)
- Blood Pressure in mmHg(64 weeks)
- Weight in Kg(64 weeks)
- Height in centimeter(64 weeks)
- Laboratory tests-Blood Routine examination(64 weeks)
- Laboratory tests-Urine Routine test(64 weeks)