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

Phase 1

Terminated

• Conditions: Advanced Solid Tumor
• Interventions: Drug: LM-108; Drug: An Anti-PD-1 Antibody

• Registration Number: NCT05255484
• Lead Sponsor: LaNova Medicines Limited

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2022-02-14
• Study First Submitted QC: 2022-02-16
• Study First Posted: 2022-02-24
• Study Start: 2022-05-26
• Status Verified: 2023-10
• Primary Completion: 2023-10-06
• Study Completion: 2023-10-06
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

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

Key

Exclusion Criteria

1. Any adverse event from prior anti-tumour therapy has not yet recovered to ≤grade 1 of CTCAE v5.0
2. Uncontrolled tumour-related pain
3. Known central nervous system (CNS)
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
5. Use of inhaled corticosteroids
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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LM-108 Dose Escalation	LM-108	Drug: LM-108 Administered intravenously
LM-108 Dose Expansion	LM-108	Drug: LM-108 Administered intravenously
LM-108 Combination Dose Escalation	An Anti-PD-1 Antibody	Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously
LM-108 Combination Dose Expansion	An Anti-PD-1 Antibody	Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously
LM-108 Combination Dose Escalation	LM-108	Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously
LM-108 Combination Dose Expansion	LM-108	Drug: LM-108 Administered intravenously Drug: An Anti-PD-1 Antibody Administered intravenously

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

University of Oklahoma; 🇺🇸 Norman, Oklahoma, United States

Gabrail Cancer and Research Center; 🇺🇸 Canton, Ohio, United States

Ocala Oncology Center; 🇺🇸 Ocala, Florida, United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States