Study of LM-102 in Subjects in Advanced Tumors

NCT04735796 | Terminated Phase 1 FDA Drug

• 1 other identifier: LM102-01-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (13)

• Number of participants with adverse events and serious adverse events

  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

  From screening up to 1 year

• Maximum tolerated dose (MTD)

  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

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

• Dose-limiting toxicities (DLT)

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

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

• Change in Vital Signs-ear temperature

  Change in vital signs-ear temperature will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Change in Vital Signs-pluse rate

  Change in vital signs-pluse rate will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Change in Vital Signs-blood pressure

  Change in vital signs-blood pressure will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Change in Electrocardiogram (ECG)-RR interval

  RR interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once. RR is the standard heart rate which calculated by 60 divided by heart rate.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Change in Electrocardiogram (ECG)-QT interval

  QT interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Change in Electrocardiogram (ECG)-QRS duration

  QRS duration of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Incidence of Abnormal Clinical Laboratory Test Results-hematology

  Number of participants with incidence of abnormal clinical lab test results like hematology will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Incidence of Abnormal Clinical Laboratory Test Results-Biochemistry

  Number of participants with incidence of abnormal clinical lab test results like Biochemistry will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Incidence of Abnormal Clinical Laboratory Test Results-Urinalysis

  Number of participants with incidence of abnormal clinical lab test results like Urinalysis will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

• Incidence of Abnormal Clinical Laboratory Test Results-Coagulation test

  Number of participants with incidence of abnormal clinical lab test results like Coagulation test will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM102

Secondary Outcomes (14)

• Area under the serum concentration versus time curve within one dosing interval (AUCtau)

  Up to 1 year

• Volume of distribution (Vd)

  Up to 1 year

• Volume of distribution at steady state (Vss)

  Up to 1 year

• Maximum serum concentration (Cmax)

  Up to 1 year

• Trough concentration before the next dose is administered (Ctrough)

  Up to 1 year

Study Arms (5)

LM102 Dose Escalation Level 1, 3mg/kg

EXPERIMENTAL

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

Drug: Drug：LM-102

LM102 Dose Escalation Level 2, 10mg/kg

EXPERIMENTAL

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

Drug: Drug：LM-102

LM102 Dose Escalation Level 3, 20mg/kg

EXPERIMENTAL

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

Drug: Drug：LM-102

LM102 Dose Escalation Level 4, 30mg/kg

EXPERIMENTAL

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

Drug: Drug：LM-102

LM102 Dose Escalation Level 5, 40mg/kg

EXPERIMENTAL

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

Drug: Drug：LM-102

Interventions

Drug：LM-102 DRUG

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, at most till by one year.

LM102 Dose Escalation Level 1, 3mg/kg; LM102 Dose Escalation Level 2, 10mg/kg; LM102 Dose Escalation Level 3, 20mg/kg; LM102 Dose Escalation Level 4, 30mg/kg; LM102 Dose Escalation Level 5, 40mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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; 2. Aged between 18 to 75 years old, male or female when sign the informed consent form (ICF); 3. 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; 4. Subjects are intolerable for available standard therapy or there is no standard available therapy; 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 with no deterioration within 2 weeks from the first dose; 6. Life expectancy ≥ 3 months; 7. 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; 8. 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;
• Liver function: Bilirubin ≤ 1.5 × ULN (Subjects with Gilbert's Syndrome are allowed if direct bilirubin is within normal limits); AST and ALT≤ 2.5 × ULN without liver metastases (≤ 5 × ULN if liver metastases are present); Albumin ≥ 2.5 g/dL;
• Kidney function: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula, see Appendix 2); Qualitative urine protein ≤ 1+ or qualitative urine protein ≥ 2+, but 24-hour urine protein \< 1g;
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%, QT interval (QTcF) ≤ 470 ms.
• \. Subjects who are able to well communicate with investigators as well as understand and adhere to the requirements of this study.

You may not qualify if:

• 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;
• Subjects who have symptomatic congestive heart failure, history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina pectoris, uncontrolled hypertension (Blood pressure still ≥ 140/90 mmHg after drug treatment), clinically significant cardiac arrhythmia or myocardial infarction within the past 6 months, etc.;
• Any adverse events from prior anti-tumor therapy have not yet recovered to ≤ grade 1 of CTCAE v5.0 (Except for some grade 2 toxicity that the investigator judges that there is no safety risk, such as alopecia, and other long term ≤ grade 2 toxicities which would not impact the administration of LM-102 and safety evaluation);
• Subjects who have uncontrolled or severe illness, including but not limited to ongoing or active infection requiring antibiotics;
• Subjects who have a history of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, or organ transplantation, or allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation;
• HIV infection, active HBV infection (HBV DNA exceeds the ULN), active HCV infection (HCV RNA exceeds the ULN);
• Male and female subjects who are unwilling to use adequate contraceptive methods (e.g, concomitant use of a spermicidal agent, barrier contraceptive, or/and intrauterine contraceptive during the study and for at least 6 months after the last dose of LM-102. (See Appendix 3 for contraceptive methods);

Sponsors & Collaborators

• LaNova Medicines Limited: lead

Study Sites (6)

Sarcoma Oncology Research Center, Cancer Center of Southern California

California City, California, 201203, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

Location

Oklahoma University- Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose level 1: 3mg/kg, enroll CLDN18.2 positive advanced solid tumors

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 3, 2021
• Study Start: May 27, 2021
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: October 26, 2022

Record last verified: 2022-10

Locations

US (6)