A Study of LNK01002 in Patients With Primary (PMF) or Secondary Myelofibrosis (PV-MF, ET-MF) or Acute Myeloid Leukemia

An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002 in Patients With Malignant Myeloid Hematologic Neoplasms

Sponsors

Lead Sponsor: Lynk Pharmaceuticals Co., Ltd

Source Lynk Pharmaceuticals Co., Ltd
Brief Summary

This multicenter, open-label, phase 1 study designed to evaluate safety and tolerability of multi-kinase inhibitor LNK01002 in patients with primary myelofibrosis (MF), or MF due to polycythemia vera (PV-MF), or essential thrombocythemia (ET-MF), or with acute myeloid leukemia (AML).

Detailed Description

This is a Phase I, open-label, dose-finding study of the triple kinase inhibitor LNK01002 in patients with myelofibrosis (MF). The study consists of two periods: the dose escalation, main period and a dose expansion period. In the dose escalation period, successive cohorts of patients with MF will be enrolled to establish the maximum tolerated dose. In the dose expansion period (dose-confirmation phase), three cohorts of patients will be enrolled: AML patients with confirmed FLT3-ITD mutations, AML patients without FLT3-ITD mutations, and patients with primary MF or PV/ET-MF. The safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of LNK01002 in patients with myelofibrosis/AML will be evaluated.

Overall Status Recruiting
Start Date 2021-04-08
Completion Date 2023-12-23
Primary Completion Date 2023-10-23
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Assessing the safety and tolerability of LNK01002 in patients with myelofibrosis 31 days
Assessing maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of LNK01002 in patients with myelofibrosis 31 days
Assessing the preliminary antitumor activity of LNK01002 24 Weeks
Secondary Outcome
Measure Time Frame
Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV-MF or ET-MF patients Day 1, Day 2, and Day 15
Enrollment 93
Condition
Intervention

Intervention Type: Drug

Intervention Name: LNK01002

Description: LNK01002 will be administrated orally.

Other Name: LNK-1000318

Eligibility

Criteria:

Inclusion Criteria: 1. Age: 18 years old or older, male or female. 2. Patients must have histologically or cytologically confirmed tumors of the following types. 3. Dose Escalation Phase: Patients with PMF, PV/ET-MF 1. Intermediate or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis which failed standard treatment. 2. Symptomatic splenomegaly 3. Not undergone splenectomy or splenic radiation therapy within 6 months prior to screening. 4. Dose expansion phase: Patients with PMF, PV/ET-MF who relapsed or are intolerant to standard treatment, and relapsed/refractory AML 5. Platelet count ≥ 100 × 10e9/L within 14 days before study drug administration 6. Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L within 14 days before study drug administration 7. Women of childbearing potential negative pregnancy test at screening. Female patients of childbearing potential, or male patients and their partners should agree to effective contraception from signing ICF until 6 months after the last dose of study drug. Exclusion Criteria: Patients who meet any of the following exclusion criteria will be excluded from the clinical study: 1. Allergic to any component of LNK01002. 2. Serum total bilirubin greater than 1.5 times the upper limit of the normal (ULN) reference range, except patients diagnosed as Gilbert's disease 3. ALT or AST higher than 3 times the ULN reference range without hepatic involvement by leukemia, which are excluded if higher than 5 times the ULN 4. Glomerular filtration rate or estimated creatinine clearance < 50 mL/min according to the Cockcroft-Gault formula; 5. Serum amylase or lipase levels higher than the ULN and considered clinically significant 6. International normalized ratio (INR) or partial activated prothrombin time (aPTT) above 1.5 times the ULN reference range 7. Known history of clinically significant liver disease, including viral or other hepatitis: a) Patients with hepatitis B or hepatitis C may be enrolled if they have a negative polymerase chain reaction (PCR) 8. Known human immunodeficiency virus (HIV) infection; 9. Clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass surgery within 6 months before enrollment, congestive heart failure with New York Heart Association (NYHA) classification of III or above, left ventricular ejection fraction (LVEF) < 50%, or uncontrolled hypertension, cardiac arrhythmia; 10. Patients with history or presence of clinically relevant non-malignant CNS disease requiring treatment 11. Patients who have received systemic antineoplastic therapy or radiotherapy within 2 weeks prior to start of study treatment: 12. Patients who have received hematopoietic stem cell transplantation (HSCT) within 60 days prior to the start of study treatment, or are receiving immunosuppressive therapy after HSCT at screening, or have graft-versus-host disease (GVHD) requiring drug control: 13. Received anti-tumor Chinese herbal medicine treatment within 1 week before the start of study treatment; 14. Received CYP3A substrates, CYP2B6 substrates, CYP2C substrates, OATP1B3 substrates, UGT1A1 inhibitors, or UGT1A3 inhibitors less than one week or 5 half-lives (whichever is longer) prior to the start of study treatment; 15. Uncontrolled, active infections requiring intravenous antibiotic treatment;

Gender:

All

Minimum Age:

18 Years

Maximum Age:

99 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Sherry Weigand, M.D., Ph.D. Study Director Lynk Pharmaceuticals Co., Ltd
Overall Contact

Last Name: Peter Langecker, M.D.

Phone: 408-656-9855

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator:
Revive Research Institute | Farmington Hills, Michigan, 48334, United States Recruiting Samuel Ceckowski 248-721-9539 [email protected] Savitha Balaraman, M.D. Principal Investigator
Revive Research Institute | Sterling Heights, Michigan, 48314, United States Recruiting Mohammed Ali 248-238-6010 [email protected] Adil Akhtar, M.D. Principal Investigator
Location Countries

United States

Verification Date

2021-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 9
Arm Group

Label: Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg

Type: Experimental

Description: Single dose of LNK01002 15 mg; followed by a 3-day observation period then 15mg BID in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg

Type: Experimental

Description: LNK01002 30 mg twice daily (BID), followed by a 3-day observation period then 30 mg BID in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 45 mg

Type: Experimental

Description: LNK01002 45 mg BID, followed by a 3-day observation period then 45 mg BID in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg

Type: Experimental

Description: LNK01002 60 mg BID, followed by a 3-day observation period then 60 mg BID in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 80 mg

Type: Experimental

Description: LNK01002 80 mg BID, followed by a 3-day observation period then 80 mg BID in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg

Type: Experimental

Description: LNK01002 100 mg BID, followed by a 3-day observation period then 100 mg BID in 28-day treatment cycles

Label: Patients with Acute Myeloid Leukemia With Mutant FLT3

Type: Experimental

Description: LNK01002 at the RP2D dose in 28-day treatment cycles

Label: Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3

Type: Experimental

Description: LNK01002 at the RP2D dose in 28-day treatment cycles

Label: Patients with Primary or Secondary Myelofibrosis

Type: Experimental

Description: LNK01002 at the RP2D dose in 28-day treatment cycles

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Intervention Model Description: An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002

Primary Purpose: Treatment

Masking: None (Open Label)

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