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

Study Overview
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Brief Summary
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A Phase I/II, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-108 as a Single Agent or in Combination with Pembrolizumab in Advanced Solid Tumors

Detailed Description
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A Phase I/II, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-108 as a Single Agent or in Combination with Pembrolizumab in Advanced Solid Tumors The study schedule includes screening visit (28 days prior to accept the investigational medicinal product (IMP)), treatment visit (accept IMP for the first time to the end of treatment (EOT)/early withdrawal), and follow-up visit (28 days after the EOT/early withdrawal).

Official Title
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A Phase I/II, Open-Label, Dose Escalation and Expansion Study of LM-108 as a Single Agent or in Combination With Pembrolizumab in Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: LM-108
* Drug: An Anti-PD-1 Antibody


Participation Criteria
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Eligibility Criteria
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Key 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 Key Exclusion Criteria: Any adverse event from prior anti-tumour therapy has not yet recovered to ≤grade 1 of CTCAE v5.0 Uncontrolled tumour-related pain Known central nervous system (CNS) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures Use of inhaled corticosteroids 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 Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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 Administered intravenously | Drug: LM-108<br>* Administered intravenously<br>|
| Experimental: LM-108 Dose Expansion<br>Drug: LM-108 Administered intravenously | Drug: LM-108<br>* Administered intravenously<br>|
| Experimental: LM-108 Combination Dose Escalation<br>Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously | Drug: LM-108<br>* Administered intravenously<br>Drug: An Anti-PD-1 Antibody<br>* Administered intravenously<br>|
| Experimental: LM-108 Combination Dose Expansion<br>Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously | Drug: LM-108<br>* Administered intravenously<br>Drug: An Anti-PD-1 Antibody<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | Incidence of adverse events | 126 weeks | 
| DLT | Incidence of dose-limiting toxicity (DLT) | 21 days | 
| SAE | Incidence of serious adverse event | 126 weeks | 
| Incidence of clinical significant in laboratory examinations | Incidence of clinical significant in laboratory examinations, including hematology, urinalysis, blood biochemistry, coagulation tests and thyroid function. | 126 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-drug antibodies to LM-108 | Incidence of anti-drug antibodies to LM-108 | 126 weeks | 
| Cmax | Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for LM-108 | 126 weeks | 
| Cmin | PK Parameter: Minimum Observed Concentration (Cmin) for LM-108 | 126 weeks | 
| Tmax | PK Parameter: Time of Maximum Observed Concentration (Tmax) for LM-108 | 126 weeks | 
| AUC | PK Parameter: Area Under the Concentration-time Curve (AUC) for LM-108 | 126 weeks | 
| Cmax,ss | PK Parameter: Steady State Maximum Concentration (Cmax,ss) | 126 weeks | 
| Cmin, ss | PK Parameter: Steady State Minimum Concentration (Cmin, ss) | 126 weeks | 
| CLss | PK Parameter: Systemic Clearance at Steady State (CLss) | 126 weeks | 
| Rac | PK Parameter: Accumulation Ratio (Rac) | 126 weeks | 
| t 1/2 | PK Parameter: Elimination Half-life (t 1/2) | 126 weeks | 
| Vss | PK Parameter: Volume of Distribution at Steady-State (Vss) | 126 weeks | 
| DF | PK Parameter: Degree of Fluctuation (DF) | 126 weeks |