Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor

NCT04465643 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: J20112IRB00215437W81XWH-22-1-0580
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate safety and feasibility of neoadjuvant nivolumab plus ipilimumab prior to standard therapy (surgery, chemotherapy or radiation therapy) in patients with Neurofibromatosis Type 1 (NF1) and newly diagnosed pre-malignant and malignant peripheral nerve sheath tumors (MPNST) for whom surgery for resection of tumor is indicated.

Conditions

Nerve Sheath Tumors

Outcome Measures

Primary Outcomes (4)

• Safety of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events

  Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  Up to 2 years

• Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events

  Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

  Up to 2 years

• Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)

  Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).

  Up to 2 years

• Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who achieve a response

  Number of participants who achieve a response (improved progression free survival).

  Up to 2 years

Secondary Outcomes (5)

• Safety as assessed by number of treatment-emergent adverse events in patients on combination nivolumab and ipilimumab with NF1, standard low, or high grade MPNST therapy

  Up to 2 years

• Objective response rate (ORR)

  Up to 2 years.

• Change in pain levels in relation to target tumor as assessed by the Numeric Rating Scale

  Baseline, Week 6, 4 months, and 8 months

• Change in pain levels in relation to target tumor as assessed by the Pain Interference Index

  Baseline, Week 6, 4 months, and 8 months

• Change in pain levels in relation to target tumor as assessed by the Patient-Reported Outcome Measurement Information System

  Baseline, Week 6, 4 months, and 8 months

Other Outcomes (39)

• Objective response rate (ORR)

  At 4 months post intervention

• Progression Free Survival

  Up to 2 years

• Tumor Response as assessed by immune markers in tumor samples

  Up to 2 years

Study Arms (1)

Immunotherapy with Nivolumab and Ipilimumab

OTHER

Nivolumab 4.5 mg/kg every 3 weeks (Q3W) x 2 Ipilimumab 1 mg/kg Q3W x 2 Nivolumab monotherapy 4.5mg/kg Q3W concurrent with standard therapy Nivolumab monotherapy should be held for at least 2 weeks before and 2 weeks after surgery

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab 4.5 mg/kg Q3W x 2

Immunotherapy with Nivolumab and Ipilimumab

Ipilimumab DRUG

Ipilimumab 1 mg/kg Q3W x 2

Immunotherapy with Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), low grade malignant peripheral nerve sheath tumor (MPNST) or high grade MPNST in accordance with the Miettinen et al diagnostic criteria via biopsy
• Plexiform neurofibroma or other tumors such as optic pathway glioma, other low-grade glioma or other neoplasm in addition to the ANNUBP, low grade MPNST or high grade MPNST that is stable (has not required treatment in the last 12 months and is not anticipated to need treatment in the next 12 months)
• Measureable disease by RECIST criteria in at least one site.
• Karnofsky Performance Scale ≥ 60%
• No contraindications for Nivolumab or Ipilimumab
• Normal organ and marrow function on routine laboratory tests
• Evidence of post-menopausal status or negative urinary/serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause
• Ability to understand and willingness of sign consent form
• Willingness to comply with the protocol for the duration of the study

You may not qualify if:

• Chemotherapy or other investigational agent for the current episode of newly diagnosed atypical neurofibroma or MPNST
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody
• Known allergy to compounds of similar chemical or biologic composition to Nivolumab or Ipilimumab
• Pregnant or breastfeeding women
• Known history of Human Immunodeficiency Virus
• Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
• Active autoimmune disease, history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications, e.g. organ, tissue, or allogenic hematopoietic stem cell transplant (HSCT) recipients. Exceptions include those with resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study. Subjects are also permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up to 4 weeks (28 days) before receiving nivolumab and ipilimumab.
• Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
• Prior radiation doses equivalent to, or greater than, 8000 centigray (cGy) to the target lesions at 200 cGy fractions at any time point
• Any radiation to the the target lesions within 6 months of enrollment
• Other concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, congestive heart failure, etc.)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator
• Congressionally Directed Medical Research Programs: collaborator
• Cancer Research and Biostatistics Clinical Trials Consortium: collaborator

Study Sites (1)

Johns Hopkins Medical Institution

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Nerve Sheath Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jaishri Blakeley, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 10, 2020
• Study Start: June 8, 2021
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: October 8, 2025

Record last verified: 2025-10

Locations

US (1)