Advanced Solid Tumor
Conditions
Brief summary
A Phase I/II, Open-Label, Dose-Escalation and Dose-Expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of LM-108, an Anti-CCR8 Monoclonal Antibody, as Monotherapy or in Combination with Antitumor Therapies in Patients with Advanced Solid Tumors
Interventions
DRUGLM-108
Administered intravenously
DRUGToripalimab
Administered intravenously
Sponsors
LaNova Medicines Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 2. Histological or cytological confirmation of recurrent or refractory advanced solid tumours, and have progressed on standard therapy, or are intolerable for available standard therapy, or there is no available standard therapy. 3. At least one measurable disease for expansion cohorts per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. 4. Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose.
Exclusion criteria
1. Have received anti-CCR8 drug treatment or other clinical study drug or treatment not on the market within 28 days prior to the first dose. 2. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0. 3. Subjects with uncontrolled tumor-related pain. 4. Subjects with known brain metastases. 5. Uncontrollable clinical third luminal effusion. 6. Known history of autoimmune disease. 7. Use of any live attenuated vaccines within 28 days. 8. Have severe cardiovascular disease. 9. Uncontrolled or severe illness. 10. History of immunodeficiency disease. 11. Active malignancies which are likely to require the treatment. 12. Child-bearing potential female. 13. Have psychiatric illness or disorders.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I Dose Escalation:Incidence of dose-limiting toxicity (DLT) | 152 Weeks |
| Phase I Dose Escalation:Incidence of serious adverse event (SAE) | 152 Weeks |
| Phase I Dose Escalation:Incidence of clinical significant in laboratory examinations, including hematology, urinalysis, blood biochemistry, coagulation tests and thyroid function. | 152 Weeks |
| Phase II Dose Expansion Cohort:Objective Response Rate (ORR) Evaluated by Researchers Based on RECIST v1.1 | 152 Weeks |
| Phase I Dose Escalation:Incidence of adverse events (AEs) | 152 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Phase II Dose Expansion Cohort:Incidence of serious adverse event (SAE) | 152 Weeks |
| Phase II Dose Expansion Cohort:Incidence of clinical significant in laboratory examinations, including hematology, urinalysis, blood biochemistry, coagulation tests and thyroid function. | 152 Weeks |
| Phase II Dose Expansion Cohort:Correlation between biomarker expression levels (FoxP3, PD-L1, CCR8, CD8) and the anti-tumor activity of LM-108 as monotherapy or in combination with anti-tumor therapies. | 152 Weeks |
| Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for LM-108 | 152 Weeks |
| PK Parameter: Time of Maximum Observed Concentration (Tmax) for LM-108 | 152 Weeks |
| PK Parameter: Area Under the Concentration-time Curve (AUC) for LM-108 | 152 Weeks |
| PK Parameter: Steady State Maximum Concentration (Cmax,ss) | 152 Weeks |
| PK Parameter: Steady State Minimum Concentration (Cmin, ss) | 152 Weeks |
| PK Parameter: Systemic Clearance at Steady State (CLss) | 152 Weeks |
| PK Parameter: Accumulation Ratio (Rac) | 152 Weeks |
| PK Parameter: Elimination Half-life (t 1/2) | 152 Weeks |
| PK Parameter: Volume of Distribution at Steady-State (Vss) | 152 Weeks |
| PK Parameter: Degree of Fluctuation (DF) | 152 Weeks |
| Phase I Dose Escalation：Preliminary anti-tumor activity：Objective Response Rate,Duration of Response, Disease Control Rate,Progression-Free Survival,and Overall Survival evaluated according to the Response Evaluation Criteria in Solid Tumors (RECISTv1.1) | 152 Weeks |
| Incidence of anti-drug antibodies to LM-108 | 152 Weeks |
| Phase I Dose Escalation：Correlation between biomarker expression levels (FoxP3, PD-L1, CCR8, CD8) and the anti-tumor activity of LM-108 as monotherapy or in combination with toripalimab. | 152 Weeks |
| Phase II Dose Expansion Cohort:Antitumor Activity: Duration of Response (DOR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS) evaluated by investigators based on RECIST v1.1; | 152 Weeks |
| Phase II Dose Expansion Cohort:Objective Response Rate (ORR), DOR, DCR, and PFS evaluated by the Independent Review Committee (IRC) based on RECIST v1.1 | 152 Weeks |
| Phase II Dose Expansion Cohort:Incidence of adverse events (AEs) | 152 Weeks |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORLin Shen
Peking University Cancer Hospital & Institute
Outcome results
None listed