1135P - Comparison of intracranial (IC) response assessment criteria in patients (pts) with melanoma brain metastases (MBM) treated with combination nivolumab (NIVO) plus ipilimumab (IPI) in CheckMate 204

Background

In CheckMate 204, NIVO + IPI showed high IC mRECIST objective response rates (ORRs) in pts with asymptomatic, unirradiated MBM and a lower but durable response in pts with symptomatic and/or steroid-requiring MBM. Response as a surrogate for progression-free survival (PFS)/overall survival (OS) has prompted the use of various response assessment criteria and cutoffs for target lesion size in MBM. In this exploratory analysis, ORRs and correlation of response to survival were examined by mRECIST, RANO-BM, RECIST, and volumetric response.

Methods

Pts with metastatic melanoma and ≥ 1 unirradiated MBM (diameter, 0.5–3 cm) received NIVO 1 mg/kg + IPI 3 mg/kg Q3W × 4, followed by NIVO 3 mg/kg Q2W for ≤ 24 mo. IC ORRs were assessed using mRECIST (5 mm target lesion cutoff), RECIST (10 mm), RANO-BM (5 or 10 mm), and volumetric response (5 or 10 mm), per blinded review. IC PFS and OS using a 6-wk landmark were compared for responders vs nonresponders.

Results

IC ORR was numerically higher with mRECIST or volumetric assessment compared with RANO-BM or RECIST (Table). Responder vs nonresponder PFS and OS were significantly better across the different assessment criteria; mRECIST and volumetric response showed the strongest correlations (Table). mRECIST responders who were not RANO-BM 5 mm responders (n = 14) had similar OS to RANO-BM 5 mm responders. Among 41 pts with only target lesions < 10 mm, mRECIST ORR, and OS for the responders, was similar to the overall CheckMate 204 ITT population.

Conclusions

This analysis supports mRECIST as a reliable assessment scale by showing strong differentiation of long-term benefit for responders vs nonresponders. Volumetric response also correlated with PFS/OS supporting future trial exploratory use. Responders with only MBM < 10 mm derived comparable PFS/OS benefit to ITT, supporting the inclusion of pts with smaller MBM in future trials. Table: 1135P

^aResponder vs nonresponder; Cox proportional hazard model was used for hazard ratio (HR) calculation. ^bVolumetric response was defined as a 65% decrease in target lesions and progression as a 73% increase.

Clinical trial identification

NCT02320058.

Editorial acknowledgement

Professional medical writing and editorial assistance were provided by Melissa Kirk, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

R. Huang: Financial Interests, Personal, Advisory Board: Vysioneer; Financial Interests, Personal, Other, Consultant: Nuvation Bio; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. P. Forsyth: Financial Interests, Personal, Speaker, Consultant, Advisor: Novocure, AbbVie, BTG, Ziopharm Oncology, Tocagen, Boehringer Ingelheim, BMS, National Brain Tumor Society, Novartis, Midatech Pharma; Financial Interests, Personal, Research Grant: Department of Defense, Pfizer, Bankhead-Coley Cancer Research, Florida Academic Cancer Center Alliance, NIH, NCI, BMS, MSCCoE, Florida Breast Cancer Foundation; Financial Interests, Personal, Financially compensated role: AbbVie, NIH, BTG, Inovio Pharmaceuticals, Physical Sciences Oncology Network, NCI, Bayer, National Cancer Research Institute, BMS, NCCN. F.S. Hodi: Financial Interests, Personal, Other, Consultant: BMS, Merck, Novartis, Genentech/Roche, CatalYm, Immunocore, Kairos, Zumator, Corner Therapeutics, Curis, AstraZeneca; Financial Interests, Personal, Advisory Board: BioEntre, Iovance, Rheos; Financial Interests, Institutional, Research Grant: BMS, Novartis; Financial Interests, Personal, Advisory Board, equity: Apricity, Bicara, Checkpoint Therapeutics. K.A. Margolin: Financial Interests, Personal, Coordinating PI, PI and advisor, Ph IIb study of CD8 PET tracer: ImaginAb; Financial Interests, Personal, Other, Consultant on ad hoc basis: Werewolf, Xilio; Financial Interests, Personal, Other, DSMB: Iovance, Elicio; Financial Interests, Institutional, Local PI, Industry-sponsored trial: Regeneron; Financial Interests, Institutional, Local PI, Industry-sponsored trial: Agenus, Moderna, Medicenna. A.P. Algazi: Financial Interests, Personal, Advisory Board: OncoSec, Onchilles, Sensei, Bluesphere, Tentarix, Venn, IAG, WWCT, Ascendis; Financial Interests, Personal, Stocks/Shares: Valitor, OncoSec, Sensei, Onchilles; Financial Interests, Personal, Local PI: BMS, Merck, AstraZeneca, Incyte, Ascendis, Genentech, Vaccinex; Financial Interests, Institutional, Research Grant: BMS, Merck, AstraZeneca, Incyte, Ascendis, Genentech, Vaccinex. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, Beigene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Nextcure, Novartis, Obsidian, Pfizer, Roche Genentech, Seagen, Sanofi-Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi/Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Rubius, Seagen, Sanofi/Regeneron, Torque, Zelluna. C.D. Lao: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Local PI, Research funding: BMS, Novartis, Genentech, OncoSec. M.B. Atkins: Financial Interests, Personal, Advisory Board: BMS, Merck, Novartis, Eisai, Aveo, Pfizer, Werewolf, Fathom, Pyxis Oncology, PACT, Elpis, X4Pharma, ValoHealth, ScholarRock, Surface, Takeda, Roche, SAB Bio, Exelixis, Iovance, COTA, Idera, Agenus, Asher Bio, AstraZeneca, Calithera, Seagen, Sanofi, OncoRe; Financial Interests, Personal, Stocks/Shares: Werewolf, Pyxis Oncology; Financial Interests, Institutional, Coordinating PI: BMS, Merck, Agenus. M. Postow: Financial Interests, Personal, Advisory Board: BMS, Chugai, Merck, Nektar, Pfizer; Financial Interests, Institutional, Coordinating PI: BMS; Financial Interests, Institutional, Local PI: Merck, Novartis. D.A. Reardon: Financial Interests, Personal, Advisory Board: Agios, AnHeart Therapeutics, Avita Biomedical, Blue Rock Therapeutics, Bristol Myers Squibb, Boston Biomedical, CureVac AG, Del Mar Pharma, DNATrix, Hoffmann-LaRoche, Ltd., ImVax, Janssen, Kiyatec, Medicenna, Neuvogen, Novartis, Novocure, Pyramid, Sumitomo Dainippon, Vivacitas Oncology, Inc-Y-Mab Therapeutics; Financial Interests, Institutional, Research Grant: Agenus, Bristol Myers Squibb, Celldex, EMD Serono, Enterome, Epitopoietic Research Corporation, Incyte, Insightec, Novartis, Omniox, Tragara; Financial Interests, Institutional, Coordinating PI: Inovio, Merck. D.J. Grootendorst: Financial Interests, Personal, Full or part-time Employment, Employee of Bristol Myers Squibb: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. M. Askelson, C. Ritchings: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Merck, RAPT Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member: Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. All other authors have declared no conflicts of interest.