Clinical Trials/NCT04735796

NCT04735796

Terminated

Phase 1

A Phase I, First-in-Human, Open-Label, Dose Escalation Study of LM-102 Injection in Subjects With CLDN18.2-Positive Advanced Solid Tumors

LaNova Medicines Limited6 sites in 1 country9 target enrollmentMay 27, 2021

ConditionsAdvanced Solid Tumors

InterventionsDrug：LM-102

DrugsDrug：LM-102

Overview

Phase: Phase 1
Intervention: Drug：LM-102
Conditions: Advanced Solid Tumors
Sponsor: LaNova Medicines Limited
Enrollment: 9
Locations: 6
Primary Endpoint: Number of participants with adverse events and serious adverse events
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed Description

This is a phase Ⅰ, first-in-human, open-label, dose escalation study to evaluate the safety and tolerability, PK, immunogenicity and preliminary anti-tumor activity of LM-102 injection in subjects with CLDN18.2-positive advanced solid tumors. Dose Escalation Traditional '3+3' escalation design will be used. Dose escalation consists of five ascending dose levels of LM-102 (3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg and 40 mg/kg). All subjects will be administered every 3 weeks (1 cycle=21 days) with a dose of LM-102 as a 2 h (120±10 min) intravenous (IV) infusion until the disease progression, intolerance, subject discontinuation/informed consent withdrawal, or at the discretion of the investigator in consultation with sponsor. After all the subjects in each cohort complete the DLT assessment, the safety monitor committee (SMC) will make decisions for dose escalations, exploring intermediate/higher doses or terminating dose escalations according to the safety, tolerability, PK and immunogenicity data. The SMC may also adjust the dosage, frequency of administration, PK sample collection plan, etc. Based upon safety, tolerability, PK, and immunogenicity, the MTD or OBD will be determined by SMC. And the RP2D will be determined based on DLTs, MTD or OBD, and the totality of the safety data throughout the study, including dose modifications and delays, PK, and immunogenicity data, etc. The study will consist of 3 periods: 1. Screening period (up to 28 days before the first dose); 2. Treatment period; 3. Follow-up period \[28 (±3) days after end of treatment (EOT)/early withdrawal or before other anti-tumor treatments (whichever occurs earlier)\]. Safety, tolerability and anti-tumor activity evaluation of LM-102 will be conducted throughout the study.

Registry

clinicaltrials.gov

Start Date

May 27, 2021

End Date

May 19, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

LaNova Medicines Limited

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects who are fully informed of the purpose, nature, method and possible adverse reactions of the study, and are willing to participate in the study and sign the informed consent document prior to any procedure;
•Aged between 18 to 75 years old, male or female when sign the informed consent form (ICF);
•Subjects must have histological or cytological confirmation of recurrent or refractory CLDN18.2-positive advanced solid tumors including but not limit to gastric and gastroesophageal junction adenocarcinoma, pancreatic carcinoma, biliary tract carcinoma, colorectal carcinoma, ovarian carcinoma;
•Subjects are intolerable for available standard therapy or there is no standard available therapy;
•Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 with no deterioration within 2 weeks from the first dose;
•Life expectancy ≥ 3 months;
•Tumor samples have CLDN18.2 membranous staining in ≥ 1% of the tumor cells with any intensity as determined by central immunohistochemistry (IHC) testing. As such, all patients must be able to provide formalin fixed and paraffin embedded archived tumor tissue samples obtained ≤ 3 years prior to screening;
•Subjects must have the following organ and marrow function in laboratory tests within 7 days from the first dose:
•PLT ≥ 90 × 109/L; ANC ≥ 1.5 × 109/L; Hemoglobin ≥ 9 g/dL, without receiving EPO, G-CSF, or GM-CSF within 14 days and blood transfusion in at least 7 days;
•Coagulation function: INR ≤ 1.5; APTT ≤ 1.5 × ULN;

Exclusion Criteria

•Subjects who have difficulties in venous blood collection or history of dizziness with blood or needles;
•Childbearing potential female (see Appendix 3 Contraceptive Methods) who have positive pregnancy test or are breast feeding;
•Subjects who known to be allergic to LM-102 or any of its excipients;
•Exposure to any IMP, or participate in any other clinical trial within 28 days prior to 1st dosing LM-102;
•Subjects with prior anti-tumor within 28 days prior to 1st dosing of LM-102, including radiotherapy (except palliative radiotherapy, beyond 14 days prior to 1st dosing of LM-102, and the toxicity has been recovered as assessed by investigator.), chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. However, the application of other small molecular targeted drugs and the herbal medicine with anti-tumor indication longer than 14 days or 5 half-life periods of the drug (whichever is longer) is acceptable;
•Subjects who have received surgical or interventional treatment within 28 days prior to 1st dosing LM-102, excluding operations or surgeries that can be recovered within 14 days prior to 1st dosing LM-102, and have been recovered by the investigator's assessment, e.g., tumor biopsy, puncture, palliative operation, rectal/gastrostomy, etc.;
•Subjects who have concurrent administration of anticoagulation agents or vitamin K antagonists;
•Subjects who have concurrent administration of therapeutic doses of heparin (prophylactic doses are acceptable);
•Subjects who have gastric outlet obstruction, persistent recurrent vomiting or uncontrolled/significant gastrointestinal hemorrhage, symptomatic peptic ulcer, or major bleeding risk in other parts of the body within 28 days prior to 1st dosing LM-102;
•Central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence that the subject's central nervous system metastasis or meningeal metastasis has not been controlled, and the investigator judges it to be unsuitable for inclusion;

Arms & Interventions

LM102 Dose Escalation Level 1, 3mg/kg

LM102 Dose Escalation Level 1, 3mg/kg, enrolled CLDN 18.2 positive advanced solid tumors

Intervention: Drug：LM-102

LM102 Dose Escalation Level 2, 10mg/kg

LM102 Dose Escalation Level 2, 10mg/kg,enrolled CLDN 18.2 positive advanced solid tumors

Intervention: Drug：LM-102

LM102 Dose Escalation Level 3, 20mg/kg

LM102 Dose Escalation Level 3, 20mg/kg,enrolled CLDN 18.2 positive advanced solid tumors

Intervention: Drug：LM-102

LM102 Dose Escalation Level 4, 30mg/kg

LM102 Dose Escalation Level 4, 30mg/kg,enrolled CLDN 18.2 positive advanced solid tumors

Intervention: Drug：LM-102

LM102 Dose Escalation Level 5, 40mg/kg

LM102 Dose Escalation Level 5, 40mg/kg,enrolled CLDN 18.2 positive advanced solid tumors

Intervention: Drug：LM-102

Outcomes

Primary Outcomes

Number of participants with adverse events and serious adverse events

Time Frame: From screening up to 1 year

The safety profile of LM102 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Maximum tolerated dose (MTD)

Time Frame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks

MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycle

Dose-limiting toxicities (DLT)

Time Frame: Cycle 1 of each cohort. Duration of one cycle is 3 weeks

DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)

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