A Study of LNK01002 in Patients With Primary or Secondary Myelofibrosis,Polycythemia Vera or Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Peter Langecker, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lynk Pharmaceuticals Co., Ltd

Must not be taking: CYP3A inhibitors, inducers

Disqualifiers: Liver disease, HIV, cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Trial Summary

What is the purpose of this trial?

This trial tests LNK01002, a drug that blocks proteins needed for cancer cell growth, in patients with certain blood cancers. It aims to find the safest dose and see how well the drug works.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received certain cancer treatments, radiotherapy, or specific herbal medicines shortly before starting the study. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug LNK01002?

The research suggests that LNK, a component related to LNK01002, plays a role in melanoma by regulating cell growth and survival, and its manipulation could enhance the effectiveness of interferon treatment. This indicates potential therapeutic benefits of targeting LNK in cancer treatment. ^{1 2 3 4 5}

How does the drug LNK01002 work differently from other treatments?

LNK01002 may involve targeting the dual leucine zipper kinase (DLK), which plays a role in neuronal responses to injury and disease, potentially offering a novel approach by influencing pathways involved in neuron protection and regeneration. ^{6 7 8 9 10}

Research Team

Linda Wei, M.D.

Principal Investigator

Lynk Pharmaceuticals Co., Ltd

Eligibility Criteria

Inclusion Criteria

You have a type of blood cancer called PMF, PV/ET-MF, or AML and have either relapsed or are unable to tolerate standard treatment.

Platelet count ≥ 100 × 10e9/L within 14 days before study drug administration

Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L within 14 days before study drug administration

Exclusion Criteria

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;

Uncontrolled, active infections requiring intravenous antibiotic treatment;

Known history of clinically significant liver disease, including viral or other hepatitis:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Successive cohorts of patients are enrolled to establish the maximum tolerated dose of LNK01002

31 days

Multiple visits for dose adjustments and monitoring

Dose Expansion

Patients are enrolled in cohorts to confirm the dose and evaluate safety, tolerability, and preliminary efficacy

24 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LNK01002

Participant Groups

Group I: Patients with Primary or Secondary Myelofibrosis,PV Experimental Treatment 1 Intervention

LNK01002 at the RP2D dose in 28-day treatment cycles

Group II: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg Experimental Treatment 1 Intervention

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

Group III: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg Experimental Treatment 1 Intervention

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

Group IV: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 260 mg Experimental Treatment 1 Intervention

LNK01002 260 mg BID, followed by a 3-day observation period then 260 mg BID in 28-day treatment cycles

Group V: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 200 mg Experimental Treatment 1 Intervention

LNK01002 200 mg BID, followed by a 3-day observation period then 200 mg BID in 28-day treatment cycles

Group VI: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 150 mg Experimental Treatment 1 Intervention

LNK01002 150 mg BID, followed by a 3-day observation period then 150 mg BID in 28-day treatment cycles

Group VII: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg Experimental Treatment 1 Intervention

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

Group VIII: Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3 Experimental Treatment 1 Intervention

LNK01002 at the RP2D dose in 28-day treatment cycles

Group IX: Patients with Acute Myeloid Leukemia With Mutant FLT3 Experimental Treatment 1 Intervention

LNK01002 at the RP2D dose in 28-day treatment cycles

Group X: Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Lynk Pharmaceuticals Co., Ltd

Lead Sponsor

Trials

7

Recruited

1,300+

References

1. England pubmed.ncbi.nlm.nih.gov

LNK suppresses interferon signaling in melanoma. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Phosphorylation of p53 by LRRK2 induces microglial tumor necrosis factor α-mediated neurotoxicity. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Leucine-Rich Repeat Kinase 2 (LRRK2) Stimulates IL-1β-Mediated Inflammatory Signaling through Phosphorylation of RCAN1. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Multitasking: Dual Leucine Zipper-Bearing Kinases in Neuronal Development and Stress Management. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

DLK silencing attenuated neuron apoptosis through JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Identification and characterization of neuronal mitogen-activated protein kinase substrates using a specific phosphomotif antibody. [2022]