Study of LM-108 as a Single Agent or in Combination With Toripalimab in Subjects With Advanced Solid Tumours

Study Overview
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Brief Summary
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This is a phase I/II, open-Label, dose-Escalation and dose-expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-108 (an Anti-CCR8 mAb) as a Single Agent or in combination with Toripalimab in Advanced Solid Tumours.

Official Title
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A Phase I/II, Open-Label, Dose-Escalation and Dose-expansion Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-108 as a Single Agent or in Combination With Toripalimab in Advanced Solid Tumours

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: LM-108
* Drug: Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 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. At least one measurable disease for expansion cohorts per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose. Exclusion Criteria: 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. Subjects with anti-tumor treatment within 21 days prior to 1st dosing of LM-108, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0. Subjects with uncontrolled tumor-related pain. Subjects with known brain metastases. Uncontrollable clinical third luminal effusion. Known history of autoimmune disease. Use of any live attenuated vaccines within 28 days. Have severe cardiovascular disease. Uncontrolled or severe illness. History of immunodeficiency disease. Active malignancies which are likely to require the treatment. Child-bearing potential female. Have psychiatric illness or disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LM-108 Dose Escalation<br> | Drug: LM-108<br>* Administered intravenously<br>|
| Experimental: LM-108 Dose Expansion<br> | Drug: LM-108<br>* Administered intravenously<br>|
| Experimental: LM-108 combination dose escalation<br> | Drug: LM-108<br>* Administered intravenously<br>Drug: Toripalimab<br>* Administered intravenously<br>|
| Experimental: LM-108 combination dose expansion<br> | Drug: LM-108<br>* Administered intravenously<br>Drug: Toripalimab<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | 152 Weeks | 
| Incidence of dose-limiting toxicity (DLT) |  | 152 Weeks | 
| Incidence of serious adverse event (SAE) |  | 152 Weeks | 
| Incidence of clinical significant in laboratory examinations, including hematology, urinalysis, blood biochemistry, coagulation tests and thyroid function. |  | 152 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Incidence of anti-drug antibodies to LM-108 |  | 152 Weeks |