JNJ-88549968 for Myeloproliferative Disorder

Recruiting in Palo Alto (17 mi)

+20 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Recent malignancies, Organ transplant, Cardiovascular, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, JNJ-88549968, to find the safest and most effective dose for patients. It aims to determine the best dosing schedule and ensure the drug's safety.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug JNJ-88549968 for treating myeloproliferative disorders?

JAK inhibitors, like ruxolitinib, have been effective in treating myeloproliferative disorders by reducing symptoms and controlling blood cell levels. These drugs target the JAK/STAT pathway, which is often overactive in these conditions, suggesting that similar treatments could be beneficial. ^{1 2 3 4 5}

What makes the drug JNJ-88549968 unique for treating myeloproliferative disorders?

JNJ-88549968 is likely a novel JAK2 inhibitor, targeting the JAK2-STAT pathway, which is crucial in myeloproliferative disorders. This drug may offer a new approach by specifically inhibiting the JAK2V617F mutation, a common driver in these conditions, potentially providing a more targeted treatment option compared to existing JAK inhibitors. ^{3 4 6 7 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with a specific mutation called CALR in their blood cells, leading to conditions like thrombocytosis and myelofibrosis. They should be able to perform daily activities with ease or only have slight limitations (ECOG <=2). The study excludes details not provided.

Inclusion Criteria

I am at least 18 years old or the legal age of majority where the study is conducted.

My blood disorder is due to a specific CALR mutation.

I can take care of myself and am up and about more than half of my waking hours.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-88549968 with dose escalation to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule based on safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy

Approximately 5 weeks

Multiple visits (in-person)

Dose Expansion

Participants receive JNJ-88549968 at the RP2D regimen determined in dose escalation

Up to 2 years

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• JNJ-88549968 (Monoclonal Antibodies)

Trial Overview The trial tests JNJ-88549968's safety and the best dose for treating certain blood disorders. It has two parts: finding the right dose (Dose Escalation) and then seeing how safe it is at that dose (Cohort Expansion).

Participant Groups

Group I: Dose Escalation (Part 1) and Dose Expansion (Part 2) Experimental Treatment 1 Intervention

In dose escalation (Part 1), participants will receive JNJ-88549968. The dose will be escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal dosing schedule(s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens. In dose expansion (Part 2), participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose escalation (Part 1).

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

The study analyzed 60 cases of myeloproliferative neoplasms (MPN) with both JAK2 V617F and BCR-ABL mutations, highlighting that these mutations can coexist, particularly in patients with chronic myelogenous leukemia (CML).

It was found that polycythemia vera (PV) was the most common type of MPN associated with these mutations, emphasizing the importance of simultaneous testing for both mutations to ensure accurate diagnosis and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of Clinical Characteristics of JAK2 V617F and BCR-ABL Double-Mutant Myeloproliferative Neoplasms]. Yan, J., Ding, YW., Wang, PY., et al.[2022]

Crizotinib effectively suppresses the proliferation of cells and JAK/STAT signaling in myeloproliferative neoplasms (MPN), showing preclinical efficacy in patient samples and mouse models with JAK2 mutations.

The combination of crizotinib with JAK inhibitors like ruxolitinib can overcome resistance to treatment, suggesting that crizotinib may be a promising option for patients with MPN who experience persistence with JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms. Gurska, LM., Okabe, R., Schurer, A., et al.[2023]

JAK inhibitors, particularly ruxolitinib, have become essential in treating classical BCR-ABL1-negative myeloproliferative neoplasms (MPN) like primary myelofibrosis (PMF) and polycythemia vera (PV), showing significant efficacy over the past several years.

Newer JAK inhibitors, such as pacritinib and Itacitinib, are being explored for their potential benefits, including reduced side effects and improved treatment outcomes, particularly in managing anemia associated with myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium. Griesshammer, M., Sadjadian, P.[2021]

INCB018424, a JAK2 inhibitor, has shown significant clinical activity in treating myelofibrosis (MF), leading to rapid reductions in spleen size and improvements in symptoms for patients taking 10-25 mg twice daily.

The treatment was generally well tolerated, with reversible thrombocytopenia occurring in 30% of patients at the higher dose, while it was not observed at the lower dose, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK2 inhibitors: A reality? A hope? Apostolidou, E., Kantarjian, HM., Verstovsek, S.[2023]

Ruxolitinib (RUX), a JAK2 inhibitor, has shown significant efficacy in treating myelofibrosis (MF) and polycythemia vera (PV), achieving a spleen volume response in over 60% of advanced MF patients and hematocrit control in about 60% of PV cases.

While RUX is effective with mild toxicity, long-term treatment may lead to a loss of spleen volume response in MF patients, and monitoring for side effects like decreased hemoglobin/platelet levels and skin tumors is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of JAK2 inhibitors in MPNs 7 years after approval. Passamonti, F., Maffioli, M.[2021]

The JAK2 V617F mutation is commonly found in patients with myeloproliferative neoplasms and leukemias, making Janus kinases important targets for new cancer therapies.

Ruxolitinib (Jakafi®) is the first approved JAK inhibitor that effectively targets JAK2 V617F signaling, and the review discusses potential combination therapies to enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms. Gäbler, K., Behrmann, I., Haan, C.[2023]

ZT55 is a highly selective inhibitor of the JAK2V617F mutation, showing a potent effect with an IC50 value of 0.031 μM, which leads to significant inhibition of the JAK-STAT signaling pathway.

In both in vitro and in vivo studies, ZT55 effectively induced apoptosis in JAK2V617F-expressing cells and suppressed tumor growth, demonstrating its potential as a therapeutic option for myeloproliferative neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2V617F against myeloproliferative neoplasms. Hu, M., Xu, C., Yang, C., et al.[2020]

In a study of 1811 patients with myeloproliferative neoplasms (MPNs), the JAK2 p.V617F mutation was found in 96.7% of those with JAK2 mutations, confirming its status as the most common mutation associated with these conditions.

The study also identified several non-p.V617F JAK2 mutations in a small percentage of patients, indicating the presence of genetic diversity in MPNs that may have implications for diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. Alghasham, N., Alnouri, Y., Abalkhail, H., et al.[2016]

References

1. China pubmed.ncbi.nlm.nih.gov

[Analysis of Clinical Characteristics of JAK2 V617F and BCR-ABL Double-Mutant Myeloproliferative Neoplasms]. [2022]

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

Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms. [2023]

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

The BCR-ABL1-negative myeloproliferative neoplasms: a review of JAK inhibitors in the therapeutic armamentarium. [2021]

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

JAK2 inhibitors: A reality? A hope? [2023]

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

The role of JAK2 inhibitors in MPNs 7 years after approval. [2021]

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

JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Discovery and evaluation of ZT55, a novel highly-selective tyrosine kinase inhibitor of JAK2V617F against myeloproliferative neoplasms. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. [2016]