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Advanced Solid TumorPhase 1NCT05001516

Study of Turning Point Therapeutics LM-302 in Patients With Advance Solid Tumors

A Phase 1 study testing LM-302 in people with Advanced Solid Tumor, run by Turning Point Therapeutics, Inc. at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A Phase I, First-in-Human, Open-Label, Dose Escalation and Expansion Study of LM-302 in Patients with CLDN18.2-Positive Advanced Solid Tumors Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor
What is being tested?
LM-302
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
7 sitesUnited States
Study dates
29 Dec 2021to 4 Jan 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 form (ICF) prior to any procedure;
  • Aged ≥18 years old when sign the ICF, male or female;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no deterioration within 2 weeks prior to the first dose;
  • Life expectancy ≥ 3 months;
  • Phase Ⅰa (Dose Escalation): Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and have progressed on standard therapy, or are intolerable for available standard therapy , or there is no available standard therapy. The advanced solid tumors include but not limit to gastric and gastroesophageal junction adenocarcinoma, esophageal adenocarcinoma, pancreatic carcinoma, biliary tract carcinoma, colorectal carcinoma, ovarian carcinoma.
  • Claudin18.2(CLDN18.2) status will be tested by central immunohistochemistry (IHC) testing for the enrolled subjects if the archived tumor tissue samples are available, and the enrolment is not dependent on the CLDN18.2's status.
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  • CLDN18.2 positive may be required for the high dose levels as determined by Safety Monitoring Committee(SMC), the subjects need to have CLDN 18.2 positive available before enrolled and dosed, and the tumor types are limited to the types listed as phase Ib (Dose expansion).
  • Phase Ib (Dose Expansion): Subjects must have histological or cytological confirmation of recurrent or refractory CLDN18.2 positive* advanced solid tumors, and have progressed on standard therapy, or are intolerable for available standard therapy , or there is no available standard therapy. The advanced solid tumors include the following or the specific tumor types that are determined by SMC:
  • Gastric and gastroesophageal junction adenocarcinoma;
  • Pancreatic carcinoma;
  • Biliary tract carcinoma;
  • Colorectal carcinoma with known Microsatellite instability-high(MSI-H)/Different Mismatch Repair(dMMR);
  • Esophageal adenocarcinoma;
  • Ovarian mucinous carcinoma;
  • CLDN18.2-positive: defined as CLDN18.2 expression confirmed by central immunohistochemistry (IHC) test and with a staining intensity of 1+ to 3+ in ≥ 10% of the tumor cell. At least 3 subjects with a staining intensity of 2+ to 3+ in ≥ 40% of the tumor cells should be included for the dose expansion stage.
  • At least one evaluable lesion (including measurable and unmeasurable) for phase Ia dose escalation, and one measurable lesion for phase Ib dose expansion, according to RECIST v1.1;
  • Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose:
  • Bone marrow reserve: Platelet count (PLT) ≥ 90 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Haemoglobin ≥ 9 g/dL, without receiving Erythropoietin(EPO), G-Colony-Stimulating Factor(CSF), or Granulocyte-Macrophage Colony Stimulating Factor(GM-CSF) within 14 days and blood transfusion including red blood cell and platelet transfusion in at least 7 days prior to first dose;
  • Coagulation function: International Normalized Ratio(INR) ≤ 1.5; Activated Partial Thromboplastin Time(APTT) ≤ 1.5 × ULN;
  • Liver function: Total bilirubin ≤ 1.5 × ULN (Subjects with Gilbert's Syndrome are allowed if total bilirubin ≤ 3 × ULN); Aspartate Transaminase(AST) and Alanine Aminotransferase(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);
  • Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; QT interval (QTcF) ≤ 480 ms;
  • Subjects who are able to communicate we

Who cannot join

  • Exposure to any IMP, or participate in any other clinical trial within 21 days prior to 1st dosing of LM-302;
  • Subjects with anti-tumor treatment within 21 days prior to 1st dosing of LM-302, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. Following treatments have different time limits:
  • Local small-scale palliative radiotherapy (bone metastasis radiotherapy to control pain) within 14 days prior to 1st dosing;
  • Oral anti-tumor therapy, including fluorouracil antitumor drugs and small molecular targeted drugs, etc. within 14 days or 5 half-life of the drug (whichever is shorter) prior to 1st dosing;
  • Traditional Chinese medicine with anti-tumor indication within 14 days prior to 1st dosing.
  • Nitrosourea or Mitomycin C within 42 days prior to 1st dosing.
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  • Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0 (Except for toxicities without safety risk judged by the investigator, such as alopecia, and other ≤ grade 2 long term toxicities);
  • Pre-existing peripheral sensory or motor neuropathy ≥ Grade 2;
  • Subjects with uncontrolled tumor-related pain. Subjects requiring analgesic treatment must be on a stable regimen before participating in the study. Symptomatic lesions amenable by palliative radiotherapy (e.g., bone metastases or metastases causing nerve damage) should be treated prior to enrolment. For the asymptomatic metastatic lesions whose further growth would likely cause functional defects or intractable pain, if appropriate, local treatment should be considered before enrolment;
  • Subjects with known central nervous system (CNS) or meningeal metastasis;
  • Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures;
  • Subjects who are allergic or hypersensitive to LM-302 (The excipients are L-Glutamic acid, L-Arginine, Trehalose dihydrate and polysorbate 80 (for injection)) or similar products;
  • Subjects who have received the treatment targeting to CLDN18.2 or Monomethyl Auristatin E(MMAE) based Antibody-Drug Conjugates (ADCs):
  • Subjects who have received the treatment with ADCs targeting to CLDN18.2 are not eligible;
  • Subjects who were intolerable to the treatment with MMAE based ADCs or anti-CLDN18.2 antibodies are not eligible, but can be enrolled if they were tolerable to the treatments and have experienced a 28-day's washout period prior to 1st dosing of LM-302;
  • For Phase Ib (Dose Expansion), subjects who were not response to the treatment with MMAE based ADCs or anti-CLDN18.2 antibodies are not eligible;
  • Administrate strong inhibitors/strong inducers of CYP3A4 within 14 days prior to 1st dosing of LM-302;
  • Subjects with known active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated in the opinion of the investigator.
  • Use of any live vaccines (e.g., against infectious diseases such as influenza, varicella, COVID-19, etc.) within 28 days prior to 1st dosing of LM-302;
  • Subjects with the history of interstitial lung disease or drug-induced interstitial lung disease/pneumonitis;
  • Subjects who are taking therapeutic doses of anticoagulants such as heparin or vitamin K antagonists (except for preventive treatment at a stable dose);
  • Subjects with gastric outlet obstruction, persistent recurrent vomiting or uncontrolled/severe gastrointestinal hemorrhage, or ulcer within 28 days prior to 1st dosing of LM-302;
  • Subjects who received major surgery or interventional treatment within 28 days prior to 1st dosing of LM-302 (excluding tumor biopsy, puncture, etc.);
  • Subjects who have other active malignancies which are likely to require the treatment;
  • Subjects who have severe cardiovascular disease, including but not limited to:
  • Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, and II-III degree atrioventricular block, etc.;
  • Thromboembolic events requiring therapeutic anticoagulation, or equipped with venous filters;
  • Cardiac insufficiency of grade III~IV according to the New York Heart Association (NYHA) standards;
  • Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months prior to 1st dosing of LM-302;
  • Clinically uncontrollable hypertension;
  • Subjects who have uncontrolled or severe illness, including but not limited to ongoing or active infection (e.g., active Corona Virus Disease 2019（COVID-19）/Severe Acute Respiratory Syndromes(SARS)-COVID-2 infection, etc.) requiring antibiotics and/or other therapeutic administration, while SARS-COVID-2 testing is not mandatory for study entry, and the testing should follow local clinical practice guidelines/standards.
  • 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 Hepatitis B Virus(HBV) and Hepatitis C Virus(HCV)infection, with the exception:
  • Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-hepatitis B core(HBc)] and absence of HBsAg), as well as with normal liver function are eligible. Otherwise, if HBV infection was indicated, those with HBV DNA < 500 IU/ML (or equivalent level) and normal liver function, combined with clinical manifestations, judged by the investigator to exclude active infection can be enrolled;
  • Subjects with positive HCV antibody but negative hepatitis C virus RNA test results and normal liver function are eligible.
  • Child-bearing potential female who have positive results in pregnancy test or are lactating;
  • Subjects who have psychiatric illness or disorders that may preclude study compliance;
  • Subject who is judged as not eligible to participate in this study by the investigator.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Local Institution - 0013

    Duarte, California, 91010

  • Local Institution - 0017

    Fullerton, California, 92835

  • Local Institution - 0015

    Houston, Texas, 77030

  • Local Institution - 0012

    Lafayette, Indiana, 47905

  • Local Institution - 0018

    New York, New York, 10016

  • Local Institution - 0016

    Oklahoma City, Oklahoma, 73120

  • Local Institution - 0020

    Paramus, New Jersey, 07652

Other trials in United States

About this study

Official title: A Phase I, First-in-Human, Open-Label, Dose Escalation and Expansion Study of TPX4589 in Patients With Claudin(CLDN)18.2-Positive Advanced Solid Tumors

A Phase I, First-in-Human, Open-Label, Dose Escalation and Expansion Study of LM-302 in Patients with CLDN18.2-Positive Advanced Solid Tumors

Read the detailed description

A Phase I, First-in-Human, Open-Label, Dose Escalation and Expansion Study of LM-302 in Patients with CLDN18.2-Positive 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).

Being tested
LM-302

What participants receive

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

  • LM-302Drug

    All subjects will be administered every 3 weeks (1 cycle=21 days) with a dose of LM-302 intravenous infusion on day 1 until meet the criteria of treatment discontinuation or withdraw, whichever occurs earlier.

Study groups in NCT05001516
Study groupRoleWhat they receive
LM302 Dose Escalation Level 1, 0.2 mg/kilogram(kg),ExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. first dose: 0.2mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=1;
Receives: Drug: LM-302
LM302 Dose Escalation Level 2, 0.4 mg/kgExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. second dose: 0.4mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=3;
Receives: Drug: LM-302
LM302 Dose Escalation Level 3, 0.8 mg/kgExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. third dose: 0.8mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=6;
Receives: Drug: LM-302
LM302 Dose Escalation Level 4, 1.6mg/kgExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. fourth dose: 1.6mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=6;
Receives: Drug: LM-302
LM302 Dose Escalation Level 5, 2.4mg/kgExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. fifth dose: 1.6mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=9;
Receives: Drug: LM-302
LM302 Dose Escalation Level 6, 2.8mg/kgExperimentalThe dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. sixth dose: 1.6mg/kg i.v. every 3 weeks (1 cycle=21 days) , n=12;
Receives: Drug: LM-302

What is being measured

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

  1. Dose limiting toxicity (DLT)

    DLT is defined as a toxicity (adverse event at least possibly related to LM302) occurring during the DLT observation period

    Measured: Cycle 1 of each cohort. Duration of one cycle is 21 days

  2. Number of participants with adverse events and serious adverse events

    The safety profile of LM302 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 the first administration in Cycle 1 date 1(C1D1)up to 1 year

  3. Change in Vital Signs-ear temperature

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

    Measured: Baseline C1D1through approximately 1 year after first administration of LM302

  4. Change in Vital Signs-pulse rate

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

    Measured: Baseline C1D1through approximately 1 year after first administration of LM302

  5. Change in Vital Signs-systolic pressure

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

    Measured: Baseline C1D1through approximately 1 year after first administration of LM302

  6. Change in Vital Signs-diastolic blood pressure

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

    Measured: Baseline C1D1through approximately 1 year after first administration of LM302

  7. Change in Physical examination-weight

    Change in Physical examination-weight will be measured with only light clothes

    Measured: Baseline C1D1through approximately 1 year after first administration of LM302

  8. 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 C1D1through approximately 1 year after first administration of LM302

  9. 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 C1D1through approximately 1 year after first administration of LM302

  10. 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 C1D1through approximately 1 year after first administration of LM302

  11. 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 C1D1through approximately 1 year after first administration of LM302

  12. Change in Electrocardiogram (ECG)-(R wave)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 C1D1through approximately 1 year after first administration of LM302

  13. 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 C1D1through approximately 1 year after first administration of LM302

  14. 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 C1D1through approximately 1 year after first administration of LM302

Secondary outcomes (13)

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

    Blood samples will be collected at time points of 0 h, immediately after infusion stop, as well as at 1 h,4 h, 8 h, 24 h, 48 h (Day 3), 168 h (Day 8), and 336 h (Day 15) after infusion stop in cycle 1 and cycle 4; 0 h in cycle 2, cycle 3 and cycle 5; pre-dose (0 h) will be collected in every other cycle for the subsequent cycles. i.e., in cycle 6, cycle 8, … etc.; at EOT/early withdraw from the study (if the EOT/early withdraw occur when PK blood sampling isn't stipulated). The timepoints of PK sample may be adjusted base on the human PK data. The blood samples for PK analysis will be collected as much as possible if the subjects end of treatment/early withdraw.

    Measured: Up to 1 year

  2. Volume of distribution at steady state (Vss)

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  3. Maximum serum concentration (Cmax)

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  4. Minimum serum concentration（Cmin）

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  5. Time to reach maximum serum concentration (Tmax)

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  6. Clearance (CL)

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  7. Terminal half-life (T1/2)

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  8. Dose proportionality

    To determine the pharmacokinetics (PK) profile of LM302

    Measured: Up to 1 year

  9. Objective response rate of LM-302.

    Preliminary anti-tumor activity of LM-302 according to RECIST v1.1 assessed by investigator: objective response rate (ORR, complete response(CR)+ partial response(PR))

    Measured: Up to 1 year

  10. Duration of response of LM-302.

    Preliminary anti-tumor activity of LM-302 according to RECIST v1.1 assessed by investigator: Duration of response (DOR)

    Measured: Up to 1 year

  11. Disease control rate of LM-302.

    Preliminary anti-tumor activity of LM-302 according to RECIST v1.1 assessed by investigator: disease control rate (DCR, CR+PR+SD)

    Measured: Up to 1 year

  12. Progression-free survival of LM-302.

    Preliminary anti-tumor activity of LM-302 according to RECIST v1.1 assessed by investigator:progression-free survival (PFS)

    Measured: Up to 1 year

  13. To assess the immunogenicity of LM-302;

    Blood samples collected for Anti-Drug Antibody(ADA) assessment will be performed at 0 h of Day 1 (within 30 min prior to infusion) in cycle 1 to Cycle 5; 0 h of Day 1 in every other cycle (within 30 min prior to infusion) for the subsequent cycles, i.e., in cycle 6, cycle 8, … etc., the EOT/early withdraw from the study and safety follow-up. Nab will be detected if necessary.

    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 posted12 Aug 2021
  2. Study start29 Dec 2021
  3. Primary completion4 Jan 2024
  4. Study completion4 Jan 2024

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
Arm1:LM302 0.2 mg/kg i.v., QW×3 weeks group; Arm2:LM302 0.4 mg/kg i.v., QW×3 weeks group; Arm3:LM302 0.8 mg/kg i.v., QW×3 weeks group; Arm4:LM302 1.6 mg/kg i.v., QW×3 weeks group; Arm5:LM302 2.4 mg/kg i.v., QW×3 weeks group; Arm6:LM302 2.8 mg/kg i.v., QW×3 weeks group;
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05001516
Sponsor's protocol ID
CA128-1033
Other IDs
CA128-1033, LM-302 (TPX4589)
Status last verified
Mar 2024
First submitted
27 Jul 2021
Last updated
17 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LM-302 in people with Advanced Solid Tumor, run by Turning Point Therapeutics, Inc. at 7 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 23 inclusion and 38 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: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose limiting toxicity (DLT) (time frame: Cycle 1 of each cohort. Duration of one cycle is 21 days). The study lists 14 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 NCT05001516.

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 17 Apr 2024.

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