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

• ClinicalTrials.gov Identifier: NCT04896112
• Recruitment Status: Recruiting
• First Posted: May 21, 2021
• Last Update Posted: June 9, 2021
• Sponsor: Lynk Pharmaceuticals Co., Ltd
• Information provided by (Responsible Party): Lynk Pharmaceuticals Co., Ltd

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis	Drug: LNK01002	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 93 participants
• 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
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002 in Patients With Malignant Myeloid Hematologic Neoplasms
• Actual Study Start Date: April 8, 2021
• Estimated Primary Completion Date: October 23, 2023
• Estimated Study Completion Date: December 23, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg; Single dose of LNK01002 15 mg; followed by a 3-day observation period then 15mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg; LNK01002 30 mg twice daily (BID), followed by a 3-day observation period then 30 mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 45 mg; LNK01002 45 mg BID, followed by a 3-day observation period then 45 mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg; LNK01002 60 mg BID, followed by a 3-day observation period then 60 mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 80 mg; LNK01002 80 mg BID, followed by a 3-day observation period then 80 mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg; LNK01002 100 mg BID, followed by a 3-day observation period then 100 mg BID in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Acute Myeloid Leukemia With Mutant FLT3; LNK01002 at the RP2D dose in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3; LNK01002 at the RP2D dose in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318
Experimental: Patients with Primary or Secondary Myelofibrosis; LNK01002 at the RP2D dose in 28-day treatment cycles	Drug: LNK01002; LNK01002 will be administrated orally.; Other Name: LNK-1000318

Outcome Measures

Primary Outcome Measures :

1. Assessing the safety and tolerability of LNK01002 in patients with myelofibrosis [ Time Frame: 31 days ]
   Assessed by monitoring the frequency, duration and severity of adverse events and serious adverse events.
2. Assessing maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of LNK01002 in patients with myelofibrosis [ Time Frame: 31 days ]
   Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be assessed based on the safety profile by the SRC
3. Assessing the preliminary antitumor activity of LNK01002 [ Time Frame: 24 Weeks ]
   The preliminary antitumor activity will be analyzed in patients with different types of malignant myeloid hematologic neoplasms by response rate using bone marrow and hematologic analyses (MF/AML) or by the MF Symptom Assessment Scale and spleen volume by MRI (MF).

Secondary Outcome Measures :

1. Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
2. Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
3. Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
4. Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
5. Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
6. Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling
7. Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV-MF or ET-MF patients [ Time Frame: Day 1, Day 2, and Day 15 ]
   Measurement will be using extensive PK sampling

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

Contacts and Locations

Contacts

Contact: Peter Langecker, M.D.; 408-656-9855; plangecker@clinipace.com

Contact: Sherry Weigand, M.D., Ph.D.; 617-678-5412; sweigand1@lynkpharma.com

Locations

United States, Michigan

Revive Research Institute; Recruiting

Farmington Hills, Michigan, United States, 48334

Contact: Samuel Ceckowski 248-721-9539 sceckowski@rev-research.com

Contact: Balaraman

Principal Investigator: Savitha Balaraman, M.D.

Revive Research Institute; Recruiting

Sterling Heights, Michigan, United States, 48314

Contact: Mohammed Ali 248-238-6010 mali@rev-research.com

Principal Investigator: Adil Akhtar, M.D.

Sponsors and Collaborators

Lynk Pharmaceuticals Co., Ltd

Investigators

• Study Director: Sherry Weigand, M.D., Ph.D.; Lynk Pharmaceuticals Co., Ltd

More Information

• Responsible Party: Lynk Pharmaceuticals Co., Ltd
• ClinicalTrials.gov Identifier: NCT04896112
• Other Study ID Numbers: LNK-1002-01; IND 153144 ( Registry Identifier: FDA )
• First Posted: May 21, 2021
• Last Update Posted: June 9, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lynk Pharmaceuticals Co., Ltd:

Acute Myeloid Leukemia; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Myeloid malignancies; Myelofibrosis

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Platelet Disorders; Blood Coagulation Disorders; Hemorrhagic Disorders