Anti-PD 1 Brain Collaboration for Patients With Melanoma Brain Metastases

NCT02374242 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: CA209-170ACTRN12614001315606ANZMTG 01.14
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this research project is to test the effectiveness of nivolumab versus nivolumab together with ipilimumab for the treatment of melanoma brain metastases. Patients are eligible to join this study if they are aged 18 years or above and have been diagnosed with melanoma with brain metastases.

Conditions

Brain Metastases; Melanoma

Keywords

Brain; Metastases; Immunotherapy; Intracranial response; Nivolumab; Ipilimumab; Biomarkers; Immune related response criteria

Outcome Measures

Primary Outcomes (1)

• Intracranial response rate

  Proportion of patients with a complete or partial response in intracranial metastases as measured using RECIST 1.1 criteria (modified for brain metastases - bm RECIST), from week 12.

  Approximately 3 years

Secondary Outcomes (11)

• Extracranial response rate

  Approximately 3 years

• Overall response rate

  Approximately 3 years

• Progression free survival in intracranial disease

  Approximately 3 years

• Progression free survival in extracranial disease

  Approximately 3 years

• Overall progression free survival

  Up to 10 years

Study Arms (3)

Cohort 1 Nivolumab Monotherapy

ACTIVE COMPARATOR

Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death. After 52 weeks, nivolumab dosing can change to 480mg every 4 weeks

Drug: Nivolumab

Cohort 2 Nivolumab Monotherapy

ACTIVE COMPARATOR

Nivolumab 3mg/kg every 2 weeks, until disease progression, withdrawn consent, unacceptable toxicity or death. After 52 weeks, nivolumab dosing can change to 480mg every 4 weeks

Drug: Nivolumab

Cohort 3 Nivolumab and Ipilimumab

ACTIVE COMPARATOR

Nivolumab 1mg/kg every 3 weeks x four doses and ipilimumab 3mg/kg every 3 weeks x four doses. After 12 weeks, nivolumab 3mg/kg alone every 2 weeks until disease progression, withdrawn consent, unacceptable toxicity or death. After 52 weeks, nivolumab dosing can change to 480mg every 4 weeks

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1/PCD-1) with immunopotentiation activity.

Also known as: Opdivo, BMS-936558

Cohort 1 Nivolumab Monotherapy; Cohort 2 Nivolumab Monotherapy; Cohort 3 Nivolumab and Ipilimumab

Ipilimumab DRUG

Ipilimumab is a recombinant, human monoclonal antibody that binds to the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of ipilimumab's effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumour immune responses.

Also known as: Yervoy, BMS-734016

Cohort 3 Nivolumab and Ipilimumab

Eligibility Criteria

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

You may qualify if:

• ≥18 years of age.
• Written informed consent
• AJCC Stage IV (any T, any N, M1c) histologically confirmed melanoma or unknown primary melanoma. Patients must have at least 1 radiological definitive brain metastasis that is ≥ 5mm and ≤40mm measurable per RECIST version 1.1 guidelines.
• In patients with prior BRAF inhibitor treatment, intracranial disease progression must be demonstrated (RECIST \>20% or new measurable brain metastases) compared with nadir of intracranial response during BRAF inhibitor treatment, and confirmed with a second MRI brain scan at any time from the beginning of the drug washout period (dabrafenib=5 days, trametinib=14 days).
• No prior localised treatment for brain metastases (eg. surgery or radiotherapy).
• Neurologically asymptomatic from brain metastases.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, and life expectancy \> 30 days.
• Able to undergo MRI with Gadolinium contrast agent.
• Adequate haematological, hepatic and renal organ function.
• Women of childbearing potential: negative serum pregnancy test and effective contraception from 14 days prior to study treatment until 23 weeks after the last dose.
• Men with female partner of childbearing potential to use effective contraception from 14 days prior to study treatment until 31 weeks after the last dose.

You may not qualify if:

• Any melanoma brain metastasis \>40mm.
• Ocular melanoma.
• Prior treatment with an anti-PD-1 or anti-PD-L1 , anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Patients with active, known or suspected autoimmune disease. Patients with 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 are permitted to enroll.
• Current systemic treatment with corticosteroids, except prednisone at nonimmunosuppressive doses of ≤ 10 mg/day (or equivalent). Past treatment for non-neurological symptoms allowed, if ceased 2 weeks prior to starting study treatment. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient on a stable dose. Non-absorbed intraarticular steroid injections will be permitted.
• Any investigational drug or other systemic drug therapy for melanoma within 28 days or 5 half-lives from baseline.
• Known to be HIV positive, or a positive test for hepatitis B and C .
• Another malignancy or concurrent malignancy unless disease-free for 3 years.
• Serious or unstable pre-existing medical conditions or other conditions that could interfere with the patient's safety, consent, or compliance.
• Pregnant or breastfeeding females.
• Administration of any form of live vaccination (such as influenza vaccine) within 30 days of starting trial and anticipated use during the trial. Administration of any other vaccine is cautionary within 30 days of starting the trial and during the trial.
• Cohort 2 - per Cohorts 1 \& 3, except patients must have at least one of the following:
• Failed prior local therapy for brain metastases (including surgery, stereotactic radiotherapy or whole brain radiotherapy) where disease has progressed per RECIST (\>20% increase in SOD or new measurable brain metastases),
• and/or;
• Have current neurological symptoms related to brain metastases. IF they have received prior local therapy for brain metastases, the disease must have progressed per RECIST (\>20% increase in SOD or new measurable brain metastases),

Sponsors & Collaborators

• Melanoma Institute Australia: lead
• Melanoma and Skin Cancer Trials Limited: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Related Publications (3)

• Long GV, Atkinson V, Lo SN, Guminski AD, Sandhu SK, Brown MP, Gonzalez M, McArthur GA, Menzies AM. Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. 2025 Mar;26(3):320-330. doi: 10.1016/S1470-2045(24)00735-6. Epub 2025 Feb 17.

  PMID: 39978375 DERIVED

• Thompson JR, Lai-Kwon J, Morton RL, Guminski AD, Gonzalez M, Atkinson V, Sandhu S, Brown MP, Menzies AM, McArthur GA, Lo SN, Long GV, Bartula I. Health-related quality of life in patients with melanoma brain metastases treated with immunotherapy. Immunotherapy. 2023 Jun;15(8):593-610. doi: 10.2217/imt-2022-0262. Epub 2023 May 2.

  PMID: 37132182 DERIVED

• Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, Menzies AM, McArthur GA. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018 May;19(5):672-681. doi: 10.1016/S1470-2045(18)30139-6. Epub 2018 Mar 27.

  PMID: 29602646 DERIVED

MeSH Terms

Conditions

Melanoma; Brain Neoplasms; Neoplasm Metastasis

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Georgina Long

  Melanoma Institute Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: February 27, 2015
• Study Start: November 4, 2014
• Primary Completion: September 4, 2017
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)