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Advanced Solid TumorsPhase 1NCT04735796

Study of LM-102 in Subjects in Advanced Tumors

A Phase 1 study testing Drug：LM-102 in people with Advanced Solid Tumors, run by LaNova Medicines Limited at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Drug：LM-102
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
6 sitesUnited States
Study dates
27 May 2021to 19 May 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. 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.
  • 9. Subjects who are able to well communicate with investigators as well as understand and adhere to the requirements of this study.

Who cannot join

  • 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.;
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  • 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;
  • 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);
  • Subjects who have psychiatric illness or social situations that would preclude study compliance;
  • Subjects who have another active malignancy which is likely to require treatment;
  • Subject who is determined as not eligible to participate in this study by the investigator.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Sarcoma Oncology Research Center, Cancer Center of Southern California

    California City, California, 201203

  • Gabrail Cancer and Research Center

    Canton, Ohio, 44718

  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Oklahoma University- Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Drug：LM-102

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Drug：LM-102Drug

    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.

Study groups in NCT04735796
Study groupRoleWhat they receive
LM102 Dose Escalation Level 1, 3mg/kgExperimentalLM102 Dose Escalation Level 1, 3mg/kg, enrolled CLDN 18.2 positive advanced solid tumors
Receives: Drug: Drug：LM-102
LM102 Dose Escalation Level 2, 10mg/kgExperimentalLM102 Dose Escalation Level 2, 10mg/kg,enrolled CLDN 18.2 positive advanced solid tumors
Receives: Drug: Drug：LM-102
LM102 Dose Escalation Level 3, 20mg/kgExperimentalLM102 Dose Escalation Level 3, 20mg/kg,enrolled CLDN 18.2 positive advanced solid tumors
Receives: Drug: Drug：LM-102
LM102 Dose Escalation Level 4, 30mg/kgExperimentalLM102 Dose Escalation Level 4, 30mg/kg,enrolled CLDN 18.2 positive advanced solid tumors
Receives: Drug: Drug：LM-102
LM102 Dose Escalation Level 5, 40mg/kgExperimentalLM102 Dose Escalation Level 5, 40mg/kg,enrolled CLDN 18.2 positive advanced solid tumors
Receives: Drug: Drug：LM-102

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From screening up to 1 year

  2. 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

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

  3. 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)

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

  4. Change in Vital Signs-ear temperature

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

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

  5. Change in Vital Signs-pluse rate

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

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

  6. Change in Vital Signs-blood pressure

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

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

  7. 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.

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

  8. 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.

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

  9. 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.

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

  10. Incidence of Abnormal Clinical Laboratory Test Results-hematology

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

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

  11. Incidence of Abnormal Clinical Laboratory Test Results-Biochemistry

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

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

  12. Incidence of Abnormal Clinical Laboratory Test Results-Urinalysis

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

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

  13. 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.

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

Secondary outcomes (14)

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

    To determine the pharmacokinetics (PK) profile of LM102

    Measured: Up to 1 year

  2. Volume of distribution (Vd)

    To determine the pharmacokinetics (PK) profile of LM102

    Measured: Up to 1 year

  3. Volume of distribution at steady state (Vss)

    To determine the pharmacokinetics (PK) profile of LM102

    Measured: Up to 1 year

  4. Maximum serum concentration (Cmax)

    To determine the PK profile of LM102 as single agent

    Measured: Up to 1 year

  5. Trough concentration before the next dose is administered (Ctrough)

    To determine the PK profile of LM102

    Measured: Up to 1 year

  6. Time to reach maximum serum concentration (Tmax)

    To determine the PK profile of LM102

    Measured: Up to 1 year

  7. Clearance (CL)

    To determine the PK profile of LM102

    Measured: Up to 1 year

  8. Terminal half-life (T1/2)

    To determine the PK profile of LM102

    Measured: Up to 1 year

  9. Dose proportionality

    To determine the PK profile of LM102

    Measured: Up to 1 year

  10. Incidence of anti-drug antibodies (ADAs)

    To assess the immunogenicity of LM102

    Measured: Up to 1 year

  11. Incidence of neutralizing antibodies (NAbs)

    To assess the immunogenicity of LM102

    Measured: Up to 1 year

  12. Objective response rate (ORR)

    To assess the preliminary antitumor activity of LM102,The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.

    Measured: Up to 1 year

  13. Best of response (BOR)

    To assess the preliminary antitumor activity of LM102

    Measured: Up to 1 year

  14. Disease control rate (DCR)

    To assess the preliminary antitumor activity of LM102

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2021
  2. Study start27 May 2021
  3. Primary completion19 May 2022
  4. Study completion19 May 2022

Why it stopped: Business strategy changed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose level 1: 3mg/kg, enroll CLDN18.2 positive advanced solid tumors
Masking
Single blind
Who is masked
Participant
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04735796
Sponsor's protocol ID
LM102-01-101
Status last verified
Oct 2022
First submitted
28 Jan 2021
Last updated
26 Oct 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Drug：LM-102 in people with Advanced Solid Tumors, run by LaNova Medicines Limited at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business strategy changed). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with adverse events and serious adverse events (time frame: From screening up to 1 year). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04735796.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022.

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