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Clinical Stage IV Cutaneous Melanoma AJCC v8Phase 2NCT03873818

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

A Phase 2 study testing Ipilimumab and Pembrolizumab in people with Clinical Stage IV Cutaneous Melanoma AJCC v8 and Metastatic Malignant Neoplasm in the Brain, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ipilimumab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
21 Feb 2019to 21 Aug 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Platelets >= 100,000/uL.
  • Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L.
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 30 L/min with creatinine levels > 1.5 x institutional ULN. GFR (glomerular filtration rate) can also be used in place of creatinine or CrCl (creatinine clearance).
  • Total bilirubin =< 1.5 ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases).
  • International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Women of child-bearing potential (WOCBP) must not be breastfeeding and must have a negative pregnancy test within 3 days prior to initiation of dosing. She must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 120 days after the last dose of study drug. WOCBP must agree to adhere to the contraceptive guidance in the protocol. Note: A female participant is eligible to participate if she is not a woman of childbearing potential as defined by the protocol.
  • Fertile men must agree to use an acceptable method of birth control as described in the protocol while on study drug and up to 120 days after the last dose of study drug and also refrain from donating sperm during this period.
  • All associated toxicity from previous or concurrent cancer therapy must be resolved (to =< grade 1 or baseline) prior to study treatment administration.
  • Steroids for physiological replacement are allowed.

Who cannot join

  • 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.
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  • 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.
  • Skin cancer exclusion: Please note that basal cell carcinoma and squamous cell carcinoma is exempt from needing resection prior to treatment. (Resection can be completed after the start of treatment).
  • 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.
  • Subjects with history of life-threatening toxicity related to prior ipilimumab adjuvant therapy except those that are unlikely to re-occur with standard countermeasures (e.g. hormone replacement after adrenal crisis).
  • Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study.
  • Non-healing wound, ulcer, or bone fracture.
  • Women who are breast-feeding or pregnant.
  • Uncontrolled intercurrent illness (i.e., active infection >= grade 2) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the subject's ability to participate.
  • History of clinically significant cardiac disease or congestive heart failure > New York Heart Association (NYHA) class 2. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
  • Investigational drug use within 14 days (or 5 half-lives, whichever is longer) of the first dose of ipilimumab and pembrolizumab.
  • Has a history of non-infectious pneumonitis that required steroids or current pneumonitis.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of Open Label Low Dose Ipilimumab in Combination With Pembrolizumab in Metastatic Melanoma Patients With Brain Metastases

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess clinical benefit rate (CBR), defined as complete response (CR) + partial response (PR) + stable disease (SD) > 6 months, in the brain in subjects with melanoma brain metastasis (MBM) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria who are treatment naive to anti-PD-1 agents in the metastatic setting (prior adjuvant anti-PD1 allowed).

SECONDARY OBJECTIVES:

  1. To assess clinical benefit rate (CBR) in the brain in subjects with MBM per modified RECIST 1.1 in patients who previously progressed on PD-1 inhibitors.

II. To assess overall survival (OS) and progression free survival (PFS). III. To evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without stereotactic radiotherapy (SRT) received prior to study entry, or on study.

IV. To evaluate cytokine levels and changes in the T-cell population in the cerebrospinal fluid (CSF) and blood in patients treated with combination low dose ipilimumab and pembrolizumab.

  1. To assess changes in relative apparent diffusion coefficient as measured by magnetic resonance imaging (MRI) as an early predictor of response.

VI. To assess changes in circulating cfDNA (cell-free deoxyribonucleic acid) as determinants of response and/or markers of early progression.

VII. To evaluate molecular and immunological changes in extracranial lesions.

OUTLINE:

Patients receive ipilimumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days, every 6 weeks for the first year, and then every 12 weeks thereafter.

Medical subject headings
Brain Neoplasms, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03873818
Study groupRoleWhat they receive
Treatment (ipilimumab, pembrolizumab)ExperimentalPatients 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.
Receives: Biological: Ipilimumab; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Baseline to 2 years

Secondary outcomes (3)

  1. CBR for Patients Who Progressed on PD-1 Inhibitors

    Assess CBR in the brain in subjects with MBM per modified RECIST 1.1 in patients who previously progressed on PD-1 inhibitors.

    Measured: Baseline to 2 years

  2. Overall Survival (OS) & Progression-free Survival (PFS)

    Assess OS and PFS.

    Measured: Baseline to 2 years

  3. Brain-specific Safety and Tolerability

    Evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without SRT received prior to study entry, or on study.

    Measured: Baseline to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2019
  2. Study start21 Feb 2019
  3. Primary completion21 Aug 2025
  4. Study completion21 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03873818
Sponsor's protocol ID
2018-0875
Other IDs
NCI-2019-00406, 2018-0875
Status last verified
Nov 2025
First submitted
19 Feb 2019
Last updated
9 Jan 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Pembrolizumab in people with Clinical Stage IV Cutaneous Melanoma AJCC v8 and Metastatic Malignant Neoplasm in the Brain, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Benefit Rate (CBR) in PD-1 naïve Patients (time frame: Baseline to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03873818.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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