TY - JOUR
T1 - A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer
T2 - Cohort 36 of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART, SWOG S1609)
AU - Adams, Sylvia
AU - Othus, Megan
AU - Patel, Sandip Pravin
AU - Miller, Kathy D.
AU - Chugh, Rashmi
AU - Schuetze, Scott M.
AU - Chamberlin, Mary D.
AU - Haley, Barbara J.
AU - Storniolo, Anna Maria V.
AU - Reddy, Mridula P.
AU - Anderson, Scott A.
AU - Zimmerman, Collin T.
AU - O’Dea, Anne P.
AU - Mirshahidi, Hamid R.
AU - Ahnert, Jordi Rodon
AU - Brescia, Frank J.
AU - Hahn, Olwen
AU - Raymond, Jane M.
AU - Biggs, David D.
AU - Connolly, Roisin M.
AU - Sharon, Elad
AU - Korde, Larissa A.
AU - Gray, Robert J.
AU - Mayerson, Edward
AU - Plets, Melissa
AU - Blanke, Charles D.
AU - Chae, Young Kwang
AU - Kurzrock, Razelle
N1 - Funding Information:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant award numbers U10CA180888, U010CA180819, U10CA180820, U10CA180821, U10180868, U10CA180794, and UG1CA233196, and in part by Bristol-Myers Squibb Company. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Bristol-Meyers Squibb Company.
Funding Information:
S. Adams reports other support from BMS during the conduct of the study. M. Othus reports grants from National Institutes of Health during the conduct of the study, as well as personal fees from Merck, Biosight, Celgene, Glycomimetics, and Daiichi Sankyo outside the submitted work. S.P. Patel reports grants and personal fees from BMS during the conduct of the study, as well as grants and personal fees from Amgen, AstraZeneca, Bristol Myers Squibb, Certis, Eli Lilly, Genentech, Illumina, Merck, Pfizer, Rakuten, and Tempus outside the submitted work. K.D. Miller reports other support from Merck, Roche/Genentech, and AstraZeneca, as well as grants from Pfizer and Astex outside the submitted work. R. Chugh reports grants and personal fees from Epizyme, Inc.; personal fees from Ipsen and Deciphera; grants from Qilu Puget Sound, AADi, Novartis, Medivation, Advenchen, Plexxikonn, Springworks, Ayala, and Mundipharma; grants and non-financial support from GlaxoSmithKline; and non-financial support from Janssen and AstraZeneca outside the submitted work. A.P. O’Dea reports personal fees from Puma Biotechnology, Pfizer, Daiichi Sankyo, AstraZeneca, and Novartis outside the submitted work. H.R. Mirshahidi reports other support from Merck and Takeda outside the submitted work. J. Rodon Ahnert reports grants and personal fees from Novartis, Spectrum Pharmaceuticals Inc., and Pfizer; personal fees from Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Pepto-myc, Roche Pharmaceuticals, Ellipses Pharma, Certera, NovellusDX, and IONC-TURA SA; personal fees and other support from Molecular Partners, Merck Sharp & Dohme and Kelun Pharmaceuticals/Klus Pharma; grants, personal fees, and other support from Bayer; grants from Ipsen, Blueprint Medicines, Tocagen, Symphogen, BioAlta, GenMab, CytomX, Kelun-Biotech, and Takeda-Miillenium; grants and other support from GlaxoSmithKline; and other support from ESMO, Department of Defense, Louisiana State University, Huntsman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute, King Abdullah International Medical Research Center, WIN Consortium, Janssen, European Journal of Cancer, VHIO/Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, SOLTI, and Elsevier outside the submitted work. R.M. Connolly reports grants from Pfizer, Genentech, Novartis, Puma Biotechnology, Merck, and Macrogenics outside the submitted work. R.J. Gray reports grants from National Cancer Institute during the conduct of the study. C.D. Blanke reports grants from NCI during the conduct of the study. Y.K. Chae reports grants and personal fees from BMS during the conduct of the study. R. Kurzrock reports grants, personal fees, non-financial support, and other support from Biological Dynamics, Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance; is a consultant or advisory board member and/or has received speaker fees from Actuate Therapeutics, Astra-Zeneca, Bicara Therapeutics, Biological Dynamics, Eisai, EOM Pharmaceuticals, Iylon, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, Roche, TD2/Volastra, Turning Point Therapeutics, and X-Biotech; has an equity interest in CureMatch Inc., CureMetrix, and IDbyDNA; serves on the board of CureMatch and CureMetrix; and is a co-founder of CureMatch outside the submitted work. No disclosures were reported by the other authors.
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2022/1/15
Y1 - 2022/1/15
N2 - Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
AB - Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
UR - http://www.scopus.com/inward/record.url?scp=85123369221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85123369221&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-2182
DO - 10.1158/1078-0432.CCR-21-2182
M3 - Article
C2 - 34716198
AN - SCOPUS:85123369221
VL - 28
SP - 271
EP - 278
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 2
ER -
