Neoantigen Vaccine + Ipilimumab for Myeloproliferative Disorder

Recruiting at 11 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: JAK1/2 inhibitors

Disqualifiers: Severe asthma, Heart condition, Diabetes, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 64 weeks

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug (VAC85135) with an existing one (ipilimumab) in patients with a type of blood cancer (MPNs). The goal is to see if this combination can help the immune system fight the cancer more effectively. Ipilimumab has shown promising activity in various cancers including melanoma.

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 coordinators or your doctor.

How is the treatment Neoantigen Vaccine + Ipilimumab different from other treatments for myeloproliferative disorder?

This treatment is unique because it combines a neoantigen vaccine targeting specific mutations in the calreticulin gene with Ipilimumab, an immune checkpoint inhibitor, to enhance the body's immune response against cancer cells. This approach aims to specifically target and eliminate malignant cells in myeloproliferative disorders, which current treatments struggle to do effectively. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Neoantigen Vaccine + Ipilimumab for Myeloproliferative Disorder?

Research suggests that immune therapies, like vaccines targeting specific proteins such as PD-L1, can enhance the body's immune response against myeloproliferative disorders. Combining these vaccines with immune checkpoint inhibitors, like Ipilimumab, may improve the anti-tumor immune response, as seen in other cancer treatments. ^{2 3 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with myeloproliferative neoplasms who are generally in good health (ECOG grade 0-2) and have certain blood and chemistry lab values within specific ranges. Participants must agree to use contraception during the study and for a period after its conclusion. Those with severe medical conditions, pregnant or breastfeeding women, individuals allergic to Ipilimumab, or those previously treated with JAK2 inhibitors cannot join.

Inclusion Criteria

I agree to follow the study's rules for using contraception.

I agree to follow the study's birth control requirements.

I can take care of myself and perform daily activities.

Exclusion Criteria

I have been treated with a JAK1/2 inhibitor before.

I am allergic or cannot take Ipilimumab due to health reasons.

Serious known clinically relevant allergies or earlier anaphylactic reactions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VAC85135 and ipilimumab for the treatment of myeloproliferative neoplasms

64 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• VAC85135

Trial Overview The study tests the safety of VAC85135 combined with Ipilimumab in treating myeloproliferative neoplasms. It aims to see how well patients tolerate this neoantigen vaccine regimen when given alongside an established immunotherapy drug.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 2 Interventions

Participants with polycythemia vera (PV) or post-polycythemia vera myelofibrosis, ET and MF will receive VAC85135 target dose IM injection with ipilimumab IV infusion at the dose(s) determined by study evaluation team (SET).

Group II: Dose Escalation Experimental Treatment 2 Interventions

Participants with essential thrombocythemia (ET) and myelofibrosis (MF) will receive VAC85135 target dose intramuscular (IM) injection in the safety lead-in cohort (Cohort 0). Participants in subsequent cohorts will receive VAC85135 target dose IM injection along with ipilimumab intravenous (IV) infusion. Ipilimumab dose may be escalated based on dose limiting toxicity (DLT) observations.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Myeloproliferative neoplasms (MPNs) require individualized treatment based on genetic mutations and disease characteristics, with JAK2, CALR, and MPL mutations playing a crucial role in diagnosis and prognosis.

Ruxolitinib is an effective second-line treatment for polycythemia vera and is used to manage symptoms in myelofibrosis, while new therapies and combination treatments are being explored to improve patient outcomes and tailor care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualizing Care for Patients With Myeloproliferative Neoplasms: Integrating Genetics, Evolving Therapies, and Patient-Specific Disease Burden. Mesa, RA., Passamonti, F.[2018]

Patients with CALR-mutated myeloproliferative neoplasms (MPNs) have a low frequency of T cells that respond to CALRMUT neoantigens due to underrepresentation of MHC-I alleles that present these antigens effectively, suggesting a potential immune evasion mechanism.

Immunization with modified heteroclitic CALRMUT peptides tailored to the MHC-I alleles of these patients successfully elicited a strong CD8+ T cell response, indicating that heteroclitic peptide-based cancer vaccines could be a promising therapeutic strategy for CALRMUT MPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine. Gigoux, M., Holmström, MO., Zappasodi, R., et al.[2023]

Citations

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

Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Cancer immune therapy for myeloid malignancies: present and future. [2020]

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

Altered immune response to the annual influenza A vaccine in patients with myeloproliferative neoplasms. [2021]

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

An arginase1- and PD-L1-derived peptide-based vaccine for myeloproliferative neoplasms: A first-in-man clinical trial. [2023]

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

Individualizing Care for Patients With Myeloproliferative Neoplasms: Integrating Genetics, Evolving Therapies, and Patient-Specific Disease Burden. [2018]

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

Immune Checkpoint Blockade Enhances Shared Neoantigen-Induced T-cell Immunity Directed against Mutated Calreticulin in Myeloproliferative Neoplasms. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Impaired Antibody Response Following the Second Dose of the BNT162b2 Vaccine in Patients With Myeloproliferative Neoplasms Receiving Ruxolitinib. [2022]

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

Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine. [2023]