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

NCT05001516 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: CA128-1033LM-302 (TPX4589)
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

Brief 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

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (14)

• Dose limiting toxicity (DLT)

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

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

• 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

  From the first administration in Cycle 1 date 1(C1D1)up to 1 year

• Change in Vital Signs-ear temperature

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

  Baseline C1D1through approximately 1 year after first administration of LM302

• Change in Vital Signs-pulse rate

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

  Baseline C1D1through approximately 1 year after first administration of LM302

• Change in Vital Signs-systolic pressure

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

  Baseline C1D1through approximately 1 year after first administration of LM302

• Change in Vital Signs-diastolic blood pressure

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

  Baseline C1D1through approximately 1 year after first administration of LM302

• Change in Physical examination-weight

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

  Baseline C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

• 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.

  Baseline C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

• 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 C1D1through approximately 1 year after first administration of LM302

Secondary Outcomes (13)

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

  Up to 1 year

• Volume of distribution at steady state (Vss)

  Up to 1 year

• Maximum serum concentration (Cmax)

  Up to 1 year

• Minimum serum concentration（Cmin）

  Up to 1 year

• Time to reach maximum serum concentration (Tmax)

  Up to 1 year

Other Outcomes (1)

• To explore the correlation between CLDN18.2 expression and anti-tumor activity of LM-302

  Up to 2 years

Study Arms (6)

LM302 Dose Escalation Level 1, 0.2 mg/kilogram(kg),

EXPERIMENTAL

The 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;

Drug: LM-302

LM302 Dose Escalation Level 2, 0.4 mg/kg

EXPERIMENTAL

The 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;

Drug: LM-302

LM302 Dose Escalation Level 3, 0.8 mg/kg

EXPERIMENTAL

The 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;

Drug: LM-302

LM302 Dose Escalation Level 4, 1.6mg/kg

EXPERIMENTAL

The 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;

Drug: LM-302

LM302 Dose Escalation Level 5, 2.4mg/kg

EXPERIMENTAL

The 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;

Drug: LM-302

LM302 Dose Escalation Level 6, 2.8mg/kg

EXPERIMENTAL

The 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;

Drug: LM-302

Interventions

LM-302 DRUG

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.

LM302 Dose Escalation Level 1, 0.2 mg/kilogram(kg),; LM302 Dose Escalation Level 2, 0.4 mg/kg; LM302 Dose Escalation Level 3, 0.8 mg/kg; LM302 Dose Escalation Level 4, 1.6mg/kg; LM302 Dose Escalation Level 5, 2.4mg/kg; LM302 Dose Escalation Level 6, 2.8mg/kg

Eligibility Criteria

• Age: 18 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 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.
• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Turning Point Therapeutics, Inc.: lead

Study Sites (7)

Local Institution - 0013

Duarte, California, 91010, United States

Location

Local Institution - 0017

Fullerton, California, 92835, United States

Location

Local Institution - 0012

Lafayette, Indiana, 47905, United States

Location

Local Institution - 0020

Paramus, New Jersey, 07652, United States

Location

Local Institution - 0018

New York, New York, 10016, United States

Location

Local Institution - 0016

Oklahoma City, Oklahoma, 73120, United States

Location

Local Institution - 0015

Houston, Texas, 77030, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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;

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 12, 2021
• Study Start: December 29, 2021
• Primary Completion: January 4, 2024
• Study Completion: January 4, 2024
• Last Updated: April 17, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)