1039MO - CheckMate 204: 3-year outcomes of treatment with combination nivolumab (NIVO) plus ipilimumab (IPI) for patients (pts) with active melanoma brain metastases (MBM)

Background

In CheckMate 204, asymptomatic pts (cohort A) with active, untreated MBM achieved high intracranial (IC) and extracranial (EC) response rates with NIVO + IPI; efficacy was lower in pts with symptomatic and/or steroid-requiring MBM (cohort B). Here, we report 3-y response and survival outcomes in both cohorts, along with first results of the blinded independent central review (BICR) of imaging data.

Methods

In this open-label, multicenter, phase II study, pts with metastatic melanoma and ≥ 1 nonirradiated brain metastasis 0.5–3 cm in diameter received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, followed by NIVO 3 mg/kg Q2W until progression or unacceptable toxicity. The primary endpoint was IC clinical benefit rate, defined as the proportion of pts with complete response (CR), partial response (PR), or stable disease (SD) ≥ 6 mo (per modified RECIST 1.1). Investigator (INV)-assessed and BICR-assessed response and PFS were evaluated along with OS.

Results

At an overall minimum follow-up of 34 mo (median follow-up: 34 mo, cohort A; 7.5 mo, cohort B), there were 101 INV-assessed asymptomatic pts (95 BICR-evaluable) and 18 symptomatic pts (17 BICR-evaluable). INV- and BICR-response rates were consistent (table), with a concordance rate among evaluable pts of 85% for cohort A and 94% for cohort B. For cohort A, 36-mo IC progression-free survival (PFS) was 54% (95% CI, 43–64) by INV and 52% (41–62) by BICR, and overall survival (OS) was 72% (62–80). For cohort B, 36-mo IC PFS was 19% (95% CI, 5–40) by INV and 28% (10–50) by BICR, and OS was 37% (14–60). No new safety signals or treatment-related deaths were reported.

Conclusions

High concordance was observed between INV- and BICR-assessed responses in this trial for both cohorts. The durable 3-y OS and PFS rates for the asymptomatic cohort support the use of first-line NIVO + IPI. Symptomatic pts with MBM remain difficult to treat, but some can derive long-term benefit from NIVO + IPI. Table: 1039MO

^aTotal patients includes 6 asymptomatic pts and 1 symptomatic pt for whom BICR data were not available. CI, confidence interval; ORR, objective response rate.

Clinical trial identification

NCT02320058.

Editorial acknowledgement

Writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano of Ashfield MedComms, an Ashfield Health Company, funded by Bristol Myers Squibb Company.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

H.A. Tawbi: Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Novartis; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Consulting/Advisory Role, Research Funding: Genentech/Roche; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role, Research Funding: Merck; Financial Interests, Personal, Advisory Role, Consulting/Advisory Role: Array BioPharma; Financial Interests, Institutional, Funding, Research Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding, Research Funding: Celgene; Financial Interests, Personal, Advisory Role, Consulting honorarium: Eisai. P.A. Forsyth: Financial Interests, Personal and Institutional, Research Grant, 1R21 grant, NIH DT Study Section grant reviewer panel, honoraria: NIH/NCI; Financial Interests, Institutional, Research Grant, Grant/research support: CDMRP; Financial Interests, Institutional, Research Grant, Grant/research support: Department of Defense; Financial Interests, Institutional, Research Grant, Grant/research support: Pfizer; Financial Interests, Institutional, Research Grant, Grant/research support: State of Florida Bankhead Coley; Financial Interests, Institutional, Research Grant, Grant/research support: Moffitt Center of Excellence Celgene Project; Financial Interests, Personal, Other, Paid consultant: AbbVie, Inc. ; Financial Interests, Personal, Other, Paid consultant, honoraria : Ziopharm; Financial Interests, Personal, Other, Paid consultant: Novellus; Financial Interests, Personal, Other, Paid consultant: NCI Neuro-Oncology Branch Peer Review; Financial Interests, Personal, Other, Paid consultant : Physical Sciences Oncology Network; Financial Interests, Personal, Other, Paid consultant, honoraria : Tocagen; Financial Interests, Personal, Other, Honoraria, Membership on advisory Committee, review panel, board membership: BTG; Financial Interests, Personal, Other, Honoraria : NCRI; Financial Interests, Personal, Other, Membership on advisory Committee, review panel, board membership: Novocure ; Financial Interests, Personal, Other, Membership on advisory Committee, review panel, board membership : Inovio; Financial Interests, Personal, Invited Speaker, Membership on advisory Committee, review panel, board membership : Bayer. 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Hodi: Financial Interests, Personal and Institutional, Advisory Role, Grant to institution; consulting; Royalties to institution: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Merck; Financial Interests, Personal, Advisory Role, Consulting: EMD Serono; Financial Interests, Personal and Institutional, Advisory Role, Consulting; grant to institution; royalties to institution: Novartis; Financial Interests, Personal, Advisory Role, Advisory Board: Surface; Financial Interests, Personal, Advisory Role, Advisory Board: Compass Therapeutics; Financial Interests, Personal, Advisory Role, Scientific Advisory Board; equity: Apricity; Financial Interests, Personal, Advisory Role, Advisor Consultant: Aduro; Financial Interests, Personal, Advisory Role, Consultant: Sanofi; Financial Interests, Personal, Advisory Role, Advisory Board; equity: Pionyr; Financial Interests, Personal, Advisory Role, Advisor: 7 Hills Pharma; Financial Interests, Personal, Other, Scientific Advisory Board; equity: Torque; Financial Interests, Personal, Advisory Board, Advisory Board: Rheos; Financial Interests, Personal, Advisory Role, Consultant: Kairos; Financial Interests, Personal, Advisory Role, Scientific Advisory Board; equity: Bicara; Financial Interests, Personal, Advisory Role, Consultant: Psioxus Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Pieris Pharmacutical; Financial Interests, Personal, Advisory Board, Advisory Board: Zumutor; Financial Interests, Personal, Advisory Role, Consultant: Corner Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Eisai; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: Checkpoint Therapeutics; Financial Interests, Personal, Advisory Role, Consultant: Idera; Financial Interests, Personal, Advisory Role, Consultant: Takeda; Financial Interests, Personal, Advisory Role, Consultant: Genentech/Roche; Financial Interests, Personal, Advisory Board, Advisory Board: Bioentre; Financial Interests, Personal, Advisory Role, Consultant: Gossamer. A. Algazi: Financial Interests, Personal and Institutional, Other, Advisor fees, stock options, travel support, clinical trial support paid to UCSF: OncoSec Medical, Inc.; Financial Interests, Personal, Stocks/Shares, Stock options: Valitor Biosciences; Financial Interests, Personal and Institutional, Research Grant, Advisory Board Member Honoraria, Clinical trial support paid to UCSF: Regeneron; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Acerta; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Amgen; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: AstraZeneca; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Dynavax; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Genentech; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Idera; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Incyte; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: ISA; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: LOXO; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Merck; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Novartis; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Sensei; Financial Interests, Institutional, Research Grant, Clinical trial support paid to UCSF: Tessa; Financial Interests, Personal, Funding, Advisory Board Member Honoraria: Array. 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Hamid: Financial Interests, Personal and Institutional, Advisory Role, Consulting : Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Aduro; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Akeso; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Amgen; Financial Interests, Personal, Advisory Role, Consulting: Beigene; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Bioatla; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Genentech; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: GlaxoSmithKline; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Immunocore; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Idera; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Incyte; Financial Interests, Personal, Advisory Role, Consulting: Janssen; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Merck; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Contracted Research for Institution: NextCure; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Speaker, Contracted Research for Institution: Novartis; Financial Interests, Personal and Institutional, Speaker’s Bureau, Consulting, Speaker, Contracted Research for Institution: Pfizer; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Speaker, Contracted Research for Institution: Sanofi Regeneron; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Seattle Genetics; Financial Interests, Personal, Advisory Role, Consulting: Tempus; Financial Interests, Personal and Institutional, Advisory Role, Consulting, Contracted Research for Institution: Zelluna; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Arcus; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: CytomX; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Exelixis; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Iovance; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Moderna; Financial Interests, Institutional, Research Grant, Contracted Research for Institution: Merck Serono. 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Reardon: Financial Interests, Institutional, Other, Research paid to DFCI: Acerta Phamaceuticals; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/Consultation: Agenus; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/Consultation: Celldex; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/consultation: EMD Serono; Financial Interests, Institutional, Other, Research paid to DFCI: Incyte; Financial Interests, Institutional, Other, Research paid to DFCI, Advisory/consultation: Inovio; Financial Interests, Institutional, Other, Research paid to DFCI: Midatech; Financial Interests, Institutional, Other, Research paid to DFCI: Omniox; Financial Interests, Institutional, Other, Research paid to DFCI: Tragara; Financial Interests, Personal, Other, Advisory/consultation: AbbVie; Financial Interests, Personal, Other, Advisory/consultation: Advantagene; Financial Interests, Personal, Other, Advisory/consultation: Amgen; Financial Interests, Personal, Other, Advisory/consultation: Bayer; Financial Interests, Personal, Other, Advisory/consultation: Bristol Myers Squibb; Financial Interests, Personal, Other, Advisory/consultation: DelMar; Financial Interests, Personal, Other, Advisory/consultation: Genentech/Roche; Financial Interests, Personal, Other, Advisory/consultation: Merck; Financial Interests, Personal, Other, Advisory/consultation: Merck KGaA; Financial Interests, Personal, Other, Advisory/consultation: Monteris; Financial Interests, Personal, Other, Advisory/consultation: Novocure; Financial Interests, Personal, Other, Advisory/consultation: Oncorus; Financial Interests, Personal, Other, Advisory/consultation: Oxigene; Financial Interests, Personal, Other, Advisory/consultation: Regeneron; Financial Interests, Personal, Other, Advisory/consultation: Stemline; Financial Interests, Personal, Other, Advisory/consultation: Taiho Oncology, Inc.; Financial Interests, Personal, Other, Advisory/consultation: Boston Biomedical; Financial Interests, Personal, Other, Advisory/consultation: Medicenna. C. Lee: Financial Interests, Personal, Stocks/Shares, Employment: Bristol Myers Squibb. T. Bas: Financial Interests, Personal, Stocks/Shares, Employment, Stock Ownership: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting/advisory role - immediate family member family member: Fiore Healthcare Advisors. All other authors have declared no conflicts of interest.