Abstract 830P
Background
Checkpoint inhibitor (CPI) treatment can induce intracranial responses in patients (pts) with melanoma metastasized to the brain (MM-BM), but very limited data exist for pts with symptomatic brain metastases as the use of corticosteroids for symptomatic relief excludes these patients from most clinical studies. The purpose of MEMBRAINS is to investigate whether treatment with CPI alone or after BRAF/MEK inhibitor induction can lead to clinical benefit for pts with MM-BM in need of steroid treatment.
Methods
This is an investigator-sponsored, multicenter, non-randomized multi-arm phase II trial. To be eligible, pts need to have MM-BM with a need for >10 mg prednisolone due to brain metastasis and a performance status 0-2. pts are enrolled in two steps; step 1) a pilot phase with enrollment of six pts in each arm, and step 2) an expansion phase with the option to enroll a total of 20 pts in a specific study arm, if at least one patient has clinical benefit defined as complete response, partial response (PR) or stable disease ≥ 6 months. Primary endpoints are progression-free survival (PFS) and overall survival (OS) rates at six months. Here we report from the pilot phase of three arms; C) ipilimumab and nivolumab (IPI-NIVO) for pts treated with a steroid dose of >10-25 mg prednisolone at baseline, D) IPI-NIVO and a steroid dose >25 mg prednisolone, or E) 4 week BRAF/MEK inhibitor induction period followed by switch to IPI-NIVO for BRAF mutated pts treated with a steroid dose of >10 mg prednisolone.
Results
A total of 18 pts were treated; six in each arm. One of six patient achieved objective response (PR) in arm C, none in arm D, and two of six patients (PR) in arm E. PFS rate at 6 months were 17% in arm C, 0% in arm D, and 33% in arm E. OS rate at 6 months was 50% in arm C, 33% in arm D, and 83% in arm E.
Conclusions
The prognosis of pts with MM-BM and a need for steroid is dismal. CPI treatment response can be obtained in pts on lower doses of steroid while daily doses of steroid above 25 mg appears incompatible with CPI benefit. However, in BRAF mutated pts a short induction treatment period with BRAF/MEK inhibitor, bridging a switch to CPI, seems to be a promising treatment strategy for this hard-to-treat patient subgroup.
Clinical trial identification
NCT03563729.
Editorial acknowledgement
Legal entity responsible for the study
I-M. Svane.
Funding
Danish Cancer Society.
Disclosure
M. Donia: Non-Financial Interests, Personal, Advisory Role: Achilles Therapeutics; Non-Financial Interests, Institutional, Research Grant: BMS, Adaptimmune ltd, MSD, Roche. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS, MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. All other authors have declared no conflicts of interest.