A phase II multi-arm study of magrolimab combinations in patients with relapsed/refractory multiple myeloma

被引:11
作者
Paul, Barry [1 ]
Liedtke, Michaela [2 ]
Khouri, Jack [3 ]
Rifkin, Robert [4 ]
Gandhi, Mitul D. [5 ]
Kin, Andrew [6 ]
Levy, Moshe Y. [7 ]
Silbermann, Rebecca [8 ]
Cottini, Francesca [9 ]
Sborov, Douglas W. [10 ]
Sandhu, Irwindeep [11 ]
Villarreal, Lyssa [12 ]
Murphy, Michael [12 ]
Gu, Lin [12 ]
Chen, Ann
Rajakumaraswamy, Nishanthan [12 ]
Usmani, Saad Z. [13 ]
机构
[1] Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC 28204 USA
[2] Stanford Canc Inst, Stanford Comprehens Canc Ctr, Stanford, CA 94305 USA
[3] Taussig Canc Inst, Dept Hematol & Med Oncol, Cleveland Clin, Cleveland Hts, OH 44195 USA
[4] Rocky Mt Canc Ctr, US Oncol Res, Denver, CO 80218 USA
[5] Virginia Canc Specialists, Gainesville, VA 20155 USA
[6] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Oncol, Detroit, MI 48201 USA
[7] Baylor Univ Med Ctr, Dept Hematol & Med Oncol, Dallas, TX 75246 USA
[8] Oregon Hlth & Sci Univ, Div Hematol Med Oncol, Portland, OR 97239 USA
[9] Ohio State Univ Comprehens Canc Ctr, Dept Internal Med, Columbus, OH 43210 USA
[10] Univ Utah, Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT 84112 USA
[11] Univ Alberta, Cross Canc Inst, Dept Oncol, Edmonton, AB T6G 1Z2, Canada
[12] Gilead Sci Inc, Foster City, CA 94404 USA
[13] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA
关键词
bortezomib; carfilzomib; CD47; daratumumab; dexamethasone; immunotherapy; magrolimab; multiple myeloma; pomalidomide; CD47; BLOCKADE; CELLS; DEXAMETHASONE; LENALIDOMIDE; THALIDOMIDE; ANALOGS;
D O I
10.2217/fon-2022-0975
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patients with relapsed/refractory MM and includes a safety run-in phase followed by a dose-expansion phase. Primary end points include the incidence of dose-limiting toxicities and adverse events (safety run-in) and the objective response rate (dose expansion).
引用
收藏
页码:7 / 17
页数:11
相关论文
共 41 条
[1]   CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin's Lymphoma [J].
Advani, Ranjana ;
Flinn, Ian ;
Popplewell, Leslie ;
Forero, Andres ;
Bartlett, Nancy L. ;
Ghosh, Nilanjan ;
Kline, Justin ;
Roschewski, Mark ;
LaCasce, Ann ;
Collins, Graham P. ;
Thu Tran ;
Lynn, Judith ;
Chen, James Y. ;
Volkmer, Jens-Peter ;
Agoram, Balaji ;
Huang, Jie ;
Majeti, Ravindra ;
Weissman, Irving L. ;
Takimoto, Chris H. ;
Chao, Mark P. ;
Smith, Sonali M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (18) :1711-1721
[2]  
American Cancer Society, 2021, DRUG THER MULT MYEL
[3]   Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy [J].
Boccadoro, Mario ;
Morgan, Gareth ;
Cavenagh, Jamie .
CANCER CELL INTERNATIONAL, 2005, 5 (1)
[4]   Recent real-world treatment patterns and outcomes in US patients with relapsed/refractory multiple myeloma [J].
Bruno, Amanda S. ;
Willson, Jenny L. ;
Opalinska, Joanna M. ;
Nelson, Jeanenne J. ;
Lunacsek, Orsolya E. ;
Stafkey-Mailey, Dana R. ;
Willey, Joanne P. .
EXPERT REVIEW OF HEMATOLOGY, 2020, 13 (09) :1017-1025
[5]   Therapeutic Targeting of the Macrophage Immune Checkpoint CD47 in Myeloid Malignancies [J].
Chao, Mark P. ;
Takimoto, Chris H. ;
Feng, Dong Dong ;
McKenna, Kelly ;
Gip, Phung ;
Liu, Jie ;
Volkmer, Jens-Peter ;
Weissman, Irving L. ;
Majeti, Ravindra .
FRONTIERS IN ONCOLOGY, 2020, 9
[6]   Programmed cell removal: a new obstacle in the road to developing cancer [J].
Chao, Mark P. ;
Majeti, Ravindra ;
Weissman, Irving L. .
NATURE REVIEWS CANCER, 2012, 12 (01) :58-67
[7]   Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47 [J].
Chao, Mark P. ;
Jaiswal, Siddhartha ;
Weissman-Tsukamoto, Rachel ;
Alizadeh, Ash A. ;
Gentles, Andrew J. ;
Volkmer, Jens ;
Weiskopf, Kipp ;
Willingham, Stephen B. ;
Raveh, Tal ;
Park, Christopher Y. ;
Majeti, Ravindra ;
Weissman, Irving L. .
SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (63)
[8]   Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma [J].
Chari, Ajai ;
Vogl, Dan T. ;
Gavriatopoulou, Maria ;
Nooka, Ajay K. ;
Yee, Andrew J. ;
Huff, Carol A. ;
Moreau, Philippe ;
Dingli, David ;
Cole, Craig ;
Lonial, Sagar ;
Dimopoulos, Meletios ;
Stewart, A. Keith ;
Richter, Joshua ;
Vij, Ravi ;
Tuchman, Sascha ;
Raab, Marc S. ;
Weisel, Katja C. ;
Delforge, Michel ;
Cornell, Robert F. ;
Kaminetzky, David ;
Hoffman, James E. ;
Costa, Luciano J. ;
Parker, Terri L. ;
Levy, Moshe ;
Schreder, Martin ;
Meuleman, Nathalie ;
Frenzel, Laurent ;
Mohty, Mohamad ;
Choquet, Sylvain ;
Schiller, Gary ;
Comenzo, Raymond L. ;
Engelhardt, Monika ;
Illmer, Thomas ;
Vlummens, Philip ;
Doyen, Chantal ;
Facon, Thierry ;
Karlin, Lionel ;
Perrot, Aurore ;
Podar, Klaus ;
Kauffman, Michael G. ;
Shacham, Sharon ;
Li, Lingling ;
Tang, Shijie ;
Picklesimer, Carla ;
Saint-Martin, Jean-Richard ;
Crochiere, Marsha ;
Chang, Hua ;
Parekh, Samir ;
Landesman, Yosef ;
Shah, Jatin .
NEW ENGLAND JOURNAL OF MEDICINE, 2019, 381 (08) :727-738
[9]   Adaptive Natural Killer Cells Facilitate Effector Functions of Daratumumab in Multiple Myeloma [J].
Cho, Hyunsoo ;
Kim, Kyung Hwan ;
Lee, Hoyoung ;
Kim, Chang Gon ;
Chung, Haerim ;
Choi, Yoon Seok ;
Park, Su-Hyung ;
Cheong, June-Won ;
Min, Yoo Hong ;
Shin, Eui-Cheol ;
Kim, Jin Seok .
CLINICAL CANCER RESEARCH, 2021, 27 (10) :2947-2958
[10]  
ClinicalTrials.gov, 2022, STUD MAGR PART SOL T