First-in-Human Study of LPM6690176 in Patients With Advanced Solid Tumors.

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: LPM6690176

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lin Shen, Doctor; Phone Number: 0086-10-88121122; Email: doctorshenlin@sina.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Contact: Lin Shen, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2 mg/m2; LPM6690176 capsules administered 2 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 4 mg/m2; LPM6690176 capsules administered 4 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 8 mg/m2; LPM6690176 capsules administered 8 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 16 mg/m2; LPM6690176 capsules administered 16 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 24 mg/m2; LPM6690176 capsules administered 24 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 36 mg/m2; LPM6690176 capsules administered 36 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024
Experimental: 48 mg/m2; LPM6690176 capsules administered 48 mg/m2 on day 1-5 (qd) every two weeks.	Drug: LPM6690176; Administered orally; Other Names: LY01024

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of dose-limiting toxicities (DLTs)	From the first dose of study drug treatment through Cycle 1 (28 days)
maximum tolerated dose (MTD) of LPM6690176	From the first dose of study drug treatment through Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR is defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 2 years
Duration of response (DOR)	DOR is defined as the time from the first determination of an objective response (CR or PR) per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first, as assessed by the investigator	Approximately 2 years
isease control rate (DCR)	DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD) per RECIST v1.1 as assessed by the investigato	Approximately 2 years
Progression-free survival (PFS)	PFS is defined as the time from the date of the first dose of study drug treatment to the date of the first documentation of progressive disease or death, whichever occurs first, as assessed by the investigator using RECIST v1.1.	Approximately 2 years
Overall survival (OS)	OS is defined as the time from the date of the first dose of study drug treatment to the date of death (due to any reason) or documented last contact	Approximately 3 years
Maximum plasma concentration	Maximum plasma concentration (Cmax) of LPM6690176 and its N-demethylated metabolite after a single dose and multiple dose	From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
Time to maximum plasma concentration	Time to maximum plasma concentration (Tmax) of LPM6690176 and its N-demethylated metabolite after a single dose and multiple dose.	From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
Area under the plasma concentration-time curve	Area under the concentration versus time curve from time zero to the last quantifiable time point (AUClast) of LPM6690176 and its N-demethylated metabolite after a single dose and multiple dose; Area under the concentration versus time curve from time 0 extrapolated to infinite time (AUCinf) of LPM6690176 and its N-demethylated metabolite after a single dose and multiple dose.	From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).
Elimination half-life	Elimination half-life (t1/2) of LPM6690176 and its N-demethylated metabolite after a single dose and multiple dose.	From Pre-dose of Cycle 1 and up to Pre-dose of Cycle 2 (28 days).

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Investigators: Principal Investigator: Lin Shen, Doctor, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LY01024/CT-CHN-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No