Low Dose Ipilimumab With Pembrolizumab in Treating Patients With Melanoma That Has Spread to the Brain

NCT03873818 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2018-0875NCI-2019-00406
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and how well low dose ipilimumab works in combination with pembrolizumab in treating patients with melanoma that has spread to the brain. Immunotherapy with monoclonal antibodies, such as ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR) in PD-1 naïve Patients

  clinical benefit rate (CBR), defined as CR + PR + SD \> 6 months, in the brain in subjects with MBM per modified RECIST 1.1 criteria who are treatment naïve to anti-PD-1 agents in metastatic setting (prior adjuvant anti-PD1 allowed).

  Baseline to 2 years

Secondary Outcomes (3)

• CBR for Patients Who Progressed on PD-1 Inhibitors

  Baseline to 2 years

• Overall Survival (OS) & Progression-free Survival (PFS)

  Baseline to 2 years

• Brain-specific Safety and Tolerability

  Baseline to 2 years

Study Arms (1)

Treatment (ipilimumab, pembrolizumab)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 4 cycles for ipilimumab and up to 35 cycles for pembrolizumab in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Pembrolizumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Treatment (ipilimumab, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (ipilimumab, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Life expectancy \> 12 weeks.
• Subjects must have signed and dated an IRB/IEC (Institutional Review Board/Independent Ethics Committee) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
• Histologically confirmed malignant melanoma with measurable metastases in the brain (\>= 0.5 cm).
• At least one measurable intracranial target lesion, which previously was not treated with local therapy (no prior stereotactic radiosurgery \[SRS\] to this lesion). Largest diameter of \>= 0.5 cm, but =\< 3 cm as determined by contrast-enhanced MRI.
• Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) OR at least 4 unstained slides with an associated pathology report for testing of tumor PD-L1 expression:
• Tumor tissue should be of good quality based on total and viable tumor content.
• Patients who do not have tissue specimens may undergo a biopsy during the screening period. Acceptable samples include core-needle biopsies for deep tumor tissue or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
• Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable.
• However, if repeat biopsy is not feasible, and no archival tissue available patient still may be enrolled
• Prior stereotactic radiotherapy (SRT) and prior excision of up to 5 MBM is permitted if there has been complete recovery, with no neurologic sequelae, and measurable lesions remain. Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable. Note: Any prior SRT to brain lesions or prior excision must have occurred \>= 2 weeks before the start of dosing for this study.
• Prior radiation to non-central nervous system (non-CNS) is allowed, and does not require a washout period for treatment initiation.
• Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning protocol therapy.
• ECOG (Eastern Cooperative Oncology Group) performance status =\< 1.
• Absolute neutrophil count \>= 1500/uL.

You may not qualify if:

• History of known leptomeningeal involvement (lumbar puncture not required).
• Previous stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing for this study. Note the stereotactic radiotherapy field must not have included the brain index lesion(s).
• Subjects previously treated with SRT \> 5 lesions in the brain
• Brain lesion size \> 3 cm.
• Prior checkpoint inhibitor therapy. Allowable prior therapy: Approved adjuvant therapies, which may include molecularly-targeted agents, IFN-·, and ipilimumab.
• Patients who received ipilimumab as adjuvant or neoadjuvant therapy must have a 6 month washout before receiving any dosing on this study.
• Cohort A: Prior anti-PD in the adjuvant setting is allowed, but washout period is 6 months.
• For Cohort B: Patients with unresectable metastatic melanoma who received either anti-PD-1 or PDL-1 in the past are eligible. Washout period a minimum 3 weeks.
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
• Subject has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for \>= 2 years are eligible.
• Has a known history of or is positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (hepatitis C virus \[HCV\] ribonucleic acid (RNA) \[qualitative\] is detected). Note: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care.
• Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
• The use of corticosteroids is not allowed for 10 days prior to initiation of therapy (based upon 5 times the expected half-life of dexamethasone) except patients who are taking steroids for physiological replacement. If alternative corticosteroid therapy has been used, consultation with the sponsor medical monitor is required to determine the washout period prior to initiating study treatment.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study initiation. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; pembrolizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Isabella C Glitza, MD,PHD
• Organization: The University of Texas MD Anderson Cancer Center

icglitza@mdanderson.org

(713) 792-2921

Study Officials

• Isabella C Glitza

  M.D. Anderson Cancer Center

  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: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: March 13, 2019
• Study Start: February 21, 2019
• Primary Completion: August 21, 2025
• Study Completion: August 21, 2025
• Last Updated: January 9, 2026
• Results First Posted: January 9, 2026

Record last verified: 2025-11

Locations

US (1)