Clinical trial NCT06240546: First-in-Human Study of LPM6690176 in Patients With Advanced Solid Tumors.
Official title: A Phase I, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LPM6690176 Capsules in Patients With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Luye Pharma Group Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-05
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a phase 1, first-in-human, open-label, dose-escalation and dose-expansion study designed to evaluate the safety and tolerability, pharmacokinetics characteristics and preliminary anti-tumor activity of LPM6690176 capsules in patients with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Able to provide a signed informed consent;
2. Age 18 \~ 75 years, male or female;
3. Patients with histologically or cytologically confirmed advanced or metastatic unresectable solid tumors, who failed or intolerant to standard anti-tumor therapy or lack of standard therapy;
4. According to RECIST 1.1 criteria,

   * Dose escalation phase: patients with at least one non-measurable lesion;
   * Dose expansion phase: patients with at least one measurable lesion;
5. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1;
6. Life expectancy≥ 3 months;
7. Adequate bone marrow, liver, kidney, metabolism and coagulation function (blood transfusion, colony stimulating factors, albumin, and blood products are not allowed to use within 14 days before enrollment);
8. Negative pregnancy test within 7 days before first dose of study drug treatment in women of childbearing age. Female patients with childbearing potential were to use effective contraception during and for 6 months after the first dose of study drug treatment. Male patients (female partners with childbearing potential) should take effective contraceptive measures during study drug treatment and until 4 months after last dose of study drug administration.

Exclusion Criteria:

1. Patients who have not recovered from AEs caused by previous anti-tumor therapy to ≤ Grade 1 (assessed according to NCI-CTCAE 5.0 criteria, excluding alopecia and ≤ Grade 2 peripheral sensory neuropathy);
2. Pleural effusion, pericardial effusion, or ascites requiring medical intervention or frequent drainage within 1 month before signed informed consent decided by the investigator;
3. Symptomatic brain metastasis, history of spinal cord compression or leptomeningeal metastasis;
4. Concomitant Diseases:

   * Any of the following diseases within 6 months before the first dose of study treatment: myocardial infarction, unstable angina, coronary artery/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, and serious arrhythmia requiring treatment;
   * Patients who require long-term anticoagulant therapy or anti-platelet therapy or require long-term use of non-steroidal anti-inflammatory drugs;
   * Patients with uncontrolled hypertension, hypertensive crisis or history of hypertensive encephalopathy;
   * Patients with increased risk of gastrointestinal ulcer or gastrointestinal bleeding tendency or gastrointestinal perforation tendency;
   * Patients with known active colitis within 8 weeks prior to screening, or diarrhea ≥4 times in 24 hours;
   * Active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks before the first dose of study drug treatment;
   * HBsAg (+) and HBV DNA≥ 1×103 or HCV (+) or HIV (+);
   * Patients who have undergone major surgical procedures 4 weeks before the first dose of study drug treatment, or have severe injury, or requiring elective major surgery during the study, or have unhealed wounds, ulcers or fractures;
   * Exclusion criterion specific to dose expansion phase: patients who have any malignancy within 5 years before the first dose of study treatment except for the specific cancer under investigation in this study (cured carcinoma in situ of the cervix, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of breast ductal are eligible).
5. Prior Medications:

   * Patients who received anti-tumor therapy within 4 weeks before the first dose of study drug treatment;
   * Received LPM6690176 capsules or other PLK-1 inhibitors therapy before enrollment;
   * Received live attenuated vaccination within 4 weeks before signed informed consent;
   * Use of strong inducers or strong inhibitors of CYP3A4 within 2 weeks or 5 half-lives of the medication before the first dose of study drug treatment;
   * Use of medications mainly metabolized by CYP2B6 within 2 weeks or 5 half-lives (which takes longer time) of the medication before the first dose of study drug treatment;
6. Patients who may receive other systemic anti-tumor therapy or local radical therapy of target lesions/non-target lesions during the study;
7. History of drug abuse, drug addiction, or alcoholism;
8. Known hypersensitivity to any component of the study drug;
9. Patients who participated in other clinical trials and received treatment within 1 month;
10. Pregnant or lactating women;
11. Other conditions that may elevate the risk of the patient or interfere the study results decided by the investigator.

Primary outcomes:
measure: Number of dose-limiting toxicities (DLTs)
timeFrame: From the first dose of study drug treatment through Cycle 1 (28 days)
measure: maximum tolerated dose (MTD) of LPM6690176
timeFrame: From the first dose of study drug treatment through Cycle 1 (28 days)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Approximately 2 years
measure: Duration of response (DOR)
timeFrame: Approximately 2 years
measure: isease control rate (DCR)
timeFrame: Approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Approximately 2 years
measure: Overall survival (OS)
timeFrame: Approximately 3 years
measure: Maximum plasma concentration
timeFrame: From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
measure: Time to maximum plasma concentration
timeFrame: From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
measure: Area under the plasma concentration-time curve
timeFrame: From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
measure: Elimination half-life
timeFrame: From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, Doctor
role: PRINCIPAL_INVESTIGATOR
References: