Ipilimumab and Nivolumab in Leptomeningeal Metastases

NCT02939300 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-136
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of two drugs as a possible treatment for Leptomeningeal Metastases. The names of the study interventions involved in this study are:

• Ipilimumab
• Nivolumab

Conditions

Leptomeningeal Carcinomatosis

Keywords

Leptomeningeal Metastases

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Survival

  Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive.

  3 months

Secondary Outcomes (6)

• Percentage of Participants With Treatment-related Adverse Events

  2 years

• Cumulative Incidence of Progressive Disease at 3 Months for Intracranial Sites

  3 months post-treatment

• Cumulative Incidence of Progressive Disease at 3 Months for Extracranial Sites

  3 months post-treatment

• Number of Participants With Leptomeningeal Disease (LMD) Response Post-Treatment

  6-9 weeks after treatment initiation

• Extracranial Progression-Free Survival

  2 years

Study Arms (1)

Combination Of Nivolumab with Ipilimumab

EXPERIMENTAL

All patients will be treated based on their primary tumor diagnosis with a combination regimen of Nivolumab and Ipilimumab. Each treatment cycle is 6 weeks; exceptions below. * Melanoma: * Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses. * Followed by Nivolumab 480 mg every 4 weeks until disease progression. Each cycle of monotherapy is defined as 8 weeks. * Non-small Cell Lung Cancer / Head and Neck Cancer: \- Nivolumab 3 mg/kg every 2 weeks, and Ipilimumab 1 mg/kg every 6 weeks. * Small Cell Lung Cancer / Breast Cancer / Bladder Cancer: * Nivolumab 1 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses. * Followed by Nivolumab 240 mg every 2 weeks until disease progression. * Renal Cell Carcinoma / Other Solid Tumors (not listed above): * Nivolumab 3 mg/kg and Ipilimumab 3 mg/kg, every 3 weeks for 4 doses. * Followed by Nivolumab 480 mg every 4 weeks until disease progression. Each cycle of monotherapy is defined as 8 weeks.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

* Melanoma: \- Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle. * Non-small Cell Lung Cancer / Head and Neck Cancer: \- Combination therapy with Nivolumab 3 mg/kg * Small Cell Lung Cancer / Breast Cancer / Bladder Cancer: \- Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 240 mg per cycle. * Renal Cell Carcinoma / Other Solid Tumors (not listed above): * Combination therapy with Nivolumab 3 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle.

Also known as: Opdivo

Combination Of Nivolumab with Ipilimumab

Ipilimumab DRUG

* Non-small Cell Lung Cancer / Head and Neck Cancer: \- Combination therapy with Ipilimumab 1 mg/kg * Small Cell Lung Cancer / Breast Cancer / Bladder Cancer: \- Combination therapy with Ipilimumab 3 mg/kg for 4 doses * Renal Cell Carcinoma / Other Solid Tumors (not listed above): * Combination therapy with Ipilimumab 3 mg/kg for 4 doses

Also known as: Yervoy

Combination Of Nivolumab with Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed disease from any solid tumor
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%)
• Life expectancy of greater than 3 weeks
• Participants must have normal organ and marrow function as defined below, all screening labs should be performed within 10 days of treatment initiation.
• Adequate Organ Function Laboratory Values:
• Unit key: mcL = microliter, ULN = upper limit normal
• Hematological
• Absolute neutrophil count (ANC) ≥1500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or Erythropoietin (EPO) dependency (within 7 days of assessment)
• Renal
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

You may not qualify if:

• Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Participants who are receiving any other investigational agents.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are 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
• Patients should be excluded if they have 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. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
• Patients should be excluded if they have had prior systemic treatment with an anti-CTLA4 antibody
• Has a known history of active TB (Bacillus Tuberculosis)
• Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). These participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Brastianos PK, Strickland MR, Lee EQ, Wang N, Cohen JV, Chukwueke U, Forst DA, Eichler A, Overmoyer B, Lin NU, Chen WY, Bardia A, Juric D, Dagogo-Jack I, White MD, Dietrich J, Nayyar N, Kim AE, Alvarez-Breckenridge C, Mahar M, Mora JL, Nahed BV, Jones PS, Shih HA, Gerstner ER, Giobbie-Hurder A, Carter SL, Oh K, Cahill DP, Sullivan RJ. Phase II study of ipilimumab and nivolumab in leptomeningeal carcinomatosis. Nat Commun. 2021 Oct 12;12(1):5954. doi: 10.1038/s41467-021-25859-y.

  PMID: 34642329 DERIVED

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Priscilla Brastianos, MD
• Organization: Massachusetts General Hospital

pbrastianos@partners.org

617-724-8770

Study Officials

• Priscilla Brastianos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 29, 2016
• First Posted: October 20, 2016
• Study Start: February 15, 2018
• Primary Completion: July 22, 2021
• Study Completion: July 22, 2021
• Last Updated: November 14, 2025
• Results First Posted: November 14, 2022

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)