What is the mechanism of action of this treatment?

The most common treatments for Myeloproliferative Neoplasms (MPNs) include immune checkpoint inhibitors and therapeutic cancer vaccines. Ipilimumab, an immune checkpoint inhibitor, works by blocking CTLA-4, a protein that downregulates the immune system, thereby enhancing the body's immune response against cancer cells. Therapeutic cancer vaccines, like the investigational VAC85135, aim to stimulate the immune system to recognize and attack tumor-specific antigens. These treatments are crucial for MPN patients as they offer a targeted approach to modulate the immune system, potentially leading to better control of the disease and improved outcomes.

What side effects are associated with this type of intervention?

Common treatments for Myeloproliferative Neoplasms (MPNs) include immunomodulatory drugs (IMiDs) like lenalidomide and thalidomide, JAK2 inhibitors, and immune checkpoint inhibitors like ipilimumab. Lenalidomide and thalidomide can cause severe birth defects, hematologic toxicity, and thromboembolic events. JAK2 inhibitors may lead to anemia, thrombocytopenia, and gastrointestinal symptoms. Ipilimumab, a CTLA-4 inhibitor, is associated with immune-related adverse events such as colitis, hepatitis, dermatitis, and endocrinopathies. These side effects highlight the need for careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for Myeloproliferative Neoplasms (MPNs), including ruxolitinib, a JAK1/2 inhibitor, which has shown efficacy in reducing spleen volume and improving symptoms in myelofibrosis patients. While ipilimumab, a CTLA-4 inhibitor, is not specifically approved for MPNs, it represents a class of immune checkpoint inhibitors that are being explored for their potential in treating various cancers, including MPNs. Other treatments like fedratinib, another JAK2 inhibitor, have also been approved for myelofibrosis, highlighting the focus on targeting specific pathways involved in the disease.

What other types of research exist?

Promising novel alternatives for MPNs patients include: 1) JAK inhibitors like ruxolitinib, especially for patients with CSF3R mutations. 2) Checkpoint inhibitors targeting PD-1/PD-L1 pathways, which are being explored in various hematological malignancies. 3) Therapeutic vaccines such as sipuleucel-T, which have shown efficacy in other cancers and could be adapted for MPNs. 4) Combination strategies involving hypomethylating agents (HMAs) and immune checkpoint inhibitors to prevent resistance and enhance immune response.

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Checkpoint Inhibitor

Neoantigen Vaccine + Ipilimumab for Myeloproliferative Disorder

Phase 1

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 or 2

Have the following chemistry laboratory values: Alanine aminotransferase (ALT) <= 3*upper limit of normal (ULN), Aspartate aminotransferase (AST) <=3*ULN, Total bilirubin <=1.5*ULN, and glomerular filtration rate >=40 mL/min

Must not have

Prior treatment with any Janus kinase 1/2 (JAK1/2) inhibitor

Known sensitivity or contraindications to the use of Ipilimumab per local prescribing information

Timeline

Screening 3 weeks

Treatment Varies

Follow Up weeks 24, 48 and eot (64 weeks)

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include typical reactions associated with vaccines such as soreness at injection site, fever, fatigue, along with Ipilimumab-related risks like immune system-related inflammation affecting various organs, skin rash, digestive issues and endocrine disorders.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and perform daily activities.

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My liver and kidney functions are within the required ranges.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ weeks 24, 48 and eot (64 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~weeks 24, 48 and eot (64 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and weeks 24, 48 and eot (64 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of Participants With Dose-limiting Toxicity (DLT)

Secondary study objectives

Number of Participants Disease Response at Weeks 24, 48 and End of Treatment (EOT) per Modified IWG-MRT Criteria

Number of Participants With Antigen-specific T-cell response

Number of Participants With Overall Response per Revised Response Criteria by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) Consensus Report

+5 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Cushingoid

10%

Tinnitus

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose ExpansionExperimental Treatment2 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 EscalationExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2014

Completed Phase 3

~3140

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Myeloproliferative Neoplasms (MPNs) include immune checkpoint inhibitors and therapeutic cancer vaccines. Ipilimumab, an immune checkpoint inhibitor, works by blocking CTLA-4, a protein that downregulates the immune system, thereby enhancing the body's immune response against cancer cells. Therapeutic cancer vaccines, like the investigational VAC85135, aim to stimulate the immune system to recognize and attack tumor-specific antigens. These treatments are crucial for MPN patients as they offer a targeted approach to modulate the immune system, potentially leading to better control of the disease and improved outcomes.

Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC).Adult T-cell Leukemia/Lymphoma: A Problem Abroad and at Home.Cancer immune therapy for myeloid malignancies: present and future.