Outcomes of patients with melanoma brain metastases (MBM) treated with standard of care therapy after being excluded from MBM-specific clinical trials

Abstract Background Brain metastases are a known complication of metastatic melanoma and often result in debilitating neurological conditions or death. Pts with MBM are typically excluded from trials, however, MBM-specific trials have been designed to assess the impact of systemic therapy in this challenging population. Combination immunotherapy has demonstrated a high rate of intracranial activity in pts with asymptomatic MBMs. However, many do not quallify during the screening period and never initiate protocol. We sought to determine the treatment patterns and therapeutic outcomes in pts considered for MBM-specific trials but screen failed before initiating treatment. Methods We reviewed the outcomes of pts considered for 2 MBM-specific trials that enrolled pts with untreated MBM at MD Anderson Cancer Center, CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Both studies had cohorts that allowed symptomatic pts or pts requiring steroids. We performed a retrospective medical record review of pts who failed screening to CM204 and BEAT-MBM. Results We initially screened 65 pts and 38 screen-failed: 17 pts (50%) for BEAT-MBM and 21 pts (68%) for CM204. Of these, 15 received Ipi, Nivo, or combination off study. 5 (33%) responded to treatment and have maintained response. 10 pts received Ipi + Nivo and 3 (30%) of these maintained durable responses. 2 received Ipi alone (13%) and 3 received Nivo alone (20%). All pts received systemic therapy before radiation. Of the 5 responders, 2 received WBXRT after Ipi + Nivo. The remaining 23 pts received either targeted therapy (6), radiation alone (2), other immunotherapy +/- radiation (3), or no treatment (12). Conclusions Given the limited number of trials available to pts with MBM and high rate of screen failure (over 50% in our population), there is an unmet need that needs to be addressed. Of those patients that fail screening, many are eligible for systemic therapy off protocol. Pts with MBM treated with Ipi + Nivo off study still experienced therapeutic benefit. Given the high rate of screen failure in pts with MBM, there is a need for modification for eligibility criteria and the screening process to expedite on-protocol therapy in this vulnerable population. Clinical trial identification CheckMate 204 (NCT03175432) and BEAT-MBM (NCT02320058). Legal entity responsible for the study The University of Texas M.D. Anderson Cancer Center. Funding The University of Texas MD Anderson Cancer Center, Bristol-Myers Squibb, Genentech. Disclosure I. Glitza Oliva: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array; Advisory / Consultancy, Research grant / Funding (self): BMS; Research grant / Funding (self): Merck. R.N. Amaria: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Iovance; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Array. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution): Reata; Research grant / Funding (institution): Novartis. P. Hwu: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Iovance Biotherapeutics; Shareholder / Stockholder / Stock options: Immatics; Research grant / Funding (institution): Genentech; Advisory / Consultancy: Dragonfly Therapeutics; Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Sanofi. M.A. Davies: Advisory / Consultancy: Glaxosmithkline; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Syndax; Advisory / Consultancy: Nanostring Technologies; Advisory / Consultancy: Array Biopharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Oncothyreon; Research grant / Funding (self): Myriad Genetics; Research grant / Funding (self): Sanofi. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glaxosmithkline. All other authors have declared no conflicts of interest.