Clinical trial NCT05518045: Study of LM-108 as a Single Agent or in Combination With Toripalimab in Subjects With Advanced Solid Tumours
Official title: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: LaNova Medicines Limited
Sponsor class: INDUSTRY
First posted: 2022-08-26
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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. Subjects with anti-tumor treatment within 21 days prior to 1st dosing of LM-108, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc.
3. Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
4. Subjects with uncontrolled tumor-related pain.
5. Subjects with known brain metastases.
6. Uncontrollable clinical third luminal effusion.
7. Known history of autoimmune disease.
8. Use of any live attenuated vaccines within 28 days.
9. Have severe cardiovascular disease.
10. Uncontrolled or severe illness.
11. History of immunodeficiency disease.
12. Active malignancies which are likely to require the treatment.
13. Child-bearing potential female.
14. Have psychiatric illness or disorders.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 152 Weeks
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: 152 Weeks
measure: Incidence of serious adverse event (SAE)
timeFrame: 152 Weeks
measure: Incidence of clinical significant in laboratory examinations, including hematology, urinalysis, blood biochemistry, coagulation tests and thyroid function.
timeFrame: 152 Weeks
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for LM-108
timeFrame: 152 Weeks
measure: PK Parameter: Time of Maximum Observed Concentration (Tmax) for LM-108
timeFrame: 152 Weeks
measure: PK Parameter: Area Under the Concentration-time Curve (AUC) for LM-108
timeFrame: 152 Weeks
measure: PK Parameter: Steady State Maximum Concentration (Cmax,ss)
timeFrame: 152 Weeks
measure: PK Parameter: Steady State Minimum Concentration (Cmin, ss)
timeFrame: 152 Weeks
measure: PK Parameter: Systemic Clearance at Steady State (CLss)
timeFrame: 152 Weeks
measure: PK Parameter: Accumulation Ratio (Rac)
timeFrame: 152 Weeks
measure: PK Parameter: Elimination Half-life (t 1/2)
timeFrame: 152 Weeks
measure: PK Parameter: Volume of Distribution at Steady-State (Vss)
timeFrame: 152 Weeks
measure: PK Parameter: Degree of Fluctuation (DF)
timeFrame: 152 Weeks
measure: Incidence of anti-drug antibodies to LM-108
timeFrame: 152 Weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen
role: PRINCIPAL_INVESTIGATOR
References: