دورية أكاديمية
An open-label, first-in-human, single agent, dose escalation study for the evaluation of safety and efficacy of SAR442085 in patients with relapsed or refractory multiple myeloma.
| العنوان: | An open-label, first-in-human, single agent, dose escalation study for the evaluation of safety and efficacy of SAR442085 in patients with relapsed or refractory multiple myeloma. |
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| المؤلفون: | Kapoor P; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Nathwani N; Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, California, USA., Jelinek T; Department of Hematooncology, University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic., Pour L; Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic., Perrot A; Department of Hematology, Institut Universitaire du Cancer de Toulouse, Toulouse, France., Dimopoulos MA; Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece., Huang SY; Department of Hematology, National Taiwan University Hospital, Taipei, Taiwan., Spicka I; First Department of Medicine, Department of Hematology, First Faculty of Medicine, Charles University and General Hospital, Prague, Czech Republic., Chhabra S; Division of Hematology and Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, Arizona, USA., Lichtman E; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Medicine, Division of Hematology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Mateos MV; Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain., Kanagavel D; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., Zhao L; Research and Development, Sanofi, Research and Development, Shanghai, China., Guillemin-Paveau H; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., Macé S; Research and Development, Sanofi, Research and Development, Vitry-sur-Seine, France., van de Velde H; Research and Development, Sanofi, Research and Development, Cambridge, Massachusetts, USA., Richardson PG; Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Multiple Myeloma Center, Boston, Massachusetts, USA. |
| المصدر: | European journal of haematology [Eur J Haematol] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Country of Publication: England NLM ID: 8703985 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0609 (Electronic) Linking ISSN: 09024441 NLM ISO Abbreviation: Eur J Haematol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2005->: Oxford : Blackwell Original Publication: Copenhagen : Munksgaard, c1987- |
| مستخلص: | Objectives: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi-centre, Phase 1, single-agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)-modified anti-CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc-gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM. Methods: This study comprised two parts: Part-A (dose-escalation involving anti-CD38 mAb pre-treated and naïve patients) and Part-B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D). Results: Thirty-seven heavily pre-treated patients were treated in Part A. Part-B (dose-expansion) was not studied. Seven dose-limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5-7·5 mg/kg. Most common treatment-emergent adverse events were infusion-related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti-CD38 mAb naïve and 4% in anti-CD38 pre-treated patients, with a median progression-free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively. Conclusions: The efficacy of SAR442085 was promising in anti-CD38 mAb naïve patients but did not extend to the larger cohort of anti-CD38 mAb pre-treated patients. This observation, along with transient high-grade thrombocytopenia, could potentially limit its clinical use. (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.) |
| References: | Mikhael J, Singh E, Rice MS. Real‐world renal function among patients with multiple myeloma in the United States. Blood Cancer J. 2021;11(5):99. Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464‐477. Bazarbachi AH, Al Hamed R, Malard F, Harousseau JL, Mohty M. Relapsed refractory multiple myeloma: a comprehensive overview. Leukemia. 2019;33(10):2343‐2357. Leleu X, Martin T, Weisel K, et al. Anti‐CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes. Ann Hematol. 2022;101(10):2123‐2137. USPI I. SARCLISA® (isatuximab‐irfc) injection, for intravenous use. Initial U.S. Approval: 2020. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761113s003lbl.pdf. USPI D. DARZALEX (daratumumab) injection, for intravenous use. Initial U.S. Approval:2015 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open‐label, randomised phase 3 trial. Lancet. 2021;397(10292):2361‐2371. Sahar Kassem BKD, El‐Murr N, Carrie N, et al. SAR442085, a novel anti‐CD38 antibody with enhanced antitumor activity against multiple myeloma. Blood. 2022;139:1160‐1176. Jelinek T, Sevcikova T, Zihala D, et al. Limited efficacy of daratumumab in multiple myeloma with extramedullary disease. Leukemia. 2022;36(1):288‐291. Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low‐dose dexamethasone versus pomalidomide and low‐dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA‐MM): a randomised, multicentre, open‐label, phase 3 study. Lancet. 2019;394(10214):2096‐2107. Richardson PG, Perrot A, San‐Miguel J, et al. Isatuximab plus pomalidomide and low‐dose dexamethasone versus pomalidomide and low‐dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA‐MM): follow‐up analysis of a randomised, phase 3 study. Lancet Oncol. 2022;23(3):416‐427. Mikhael J, Belhadj‐Merzoug K, Hulin C, et al. A phase 2 study of isatuximab monotherapy in patients with multiple myeloma who are refractory to daratumumab. Blood Cancer J. 2021;11(5):89. Dimopoulos M, Bringhen S, Anttila P, et al. Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Blood. 2021;137(9):1154‐1165. Casneuf T, Xu XS, Adams HC III, et al. Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma. Blood Adv. 2017;1(23):2105‐2114. Storek J, Dawson MA, Maloney DG. Normal T, B, and NK cell counts in healthy donors at 1 year after blood stem cell harvesting. Blood. 2000;95(9):2993‐2994. Erdem GU, Dogan M, Demirci NS, Zengin N. Oxaliplatin‐induced acute thrombocytopenia. J Cancer Res Ther. 2016;12(2):509‐514. Omura Y, Shimazu H, Takahashi T. Rituximab‐induced acute thrombocytopenia in a patient with follicular lymphoma: a case report and review of the literature. Intern Med. 2018;57(8):1151‐1154. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment‐refractory multiple myeloma (SIRIUS): an open‐label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551‐1560. Sunami K, Suzuki K, Ri M, et al. Isatuximab monotherapy in relapsed/refractory multiple myeloma: a Japanese, multicenter, phase 1/2, safety and efficacy study. Cancer Sci. 2020;111(12):4526‐4539. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207‐1219. Luo C, Wu G, Huang X, et al. Efficacy and safety of new anti‐CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B‐cell non‐Hodgkin lymphomas: a systematic review and meta‐analysis. Sci Rep. 2021;11(1):3255. Klisovic RB, Leung WH, Brugger W, et al. A phase 2a, single‐arm, open‐label study of tafasitamab, a humanized, Fc‐modified, anti‐CD19 antibody, in patients with relapsed/refractory B‐precursor cell acute lymphoblastic leukemia. Cancer. 2021;127(22):4190‐4197. Shitara K, Ueha S, Shichino S, et al. First‐in‐human phase 1 study of IT1208, a defucosylated humanized anti‐CD4 depleting antibody, in patients with advanced solid tumors. J Immunother Cancer. 2019;7(1):195. Nooka AK, Joseph NS, Kaufman JL, et al. Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: utility of re‐treatment with daratumumab among refractory patients. Cancer. 2019;125(17):2991‐3000. Perez de Acha O, Reiman L, Jayabalan DS, et al. CD38 antibody re‐treatment in daratumumab‐refractory multiple myeloma after time on other therapies. Blood Adv. 2023;7(21):6430‐6440. Abdallah A‐O, Mahmoudjafari Z, Ahmed N, et al. Clinical efficacy of retreatment of daratumumab‐based therapy (D2) in daratumumab‐refractory multiple myeloma. Eur J Haematol. 2023;110(6):626‐632. Hulin C, Perrot A, Macro M, et al. Retreatment of patients with anti CD38‐based combinations in multiple myeloma in real‐life: results from the Emmy cohort study. Blood. 2022;140(Supplement 1):7133‐7135. Kastritis E, Theodorakakou F, Ntanasis‐Stathopoulos I, et al. Management and outcomes of anti‐CD38 refractory myeloma patients: the impact of retreatment and of subsequent therapies. Blood. 2022;140(Supplement 1):7324‐7325. An G. Concept of pharmacologic target‐mediated drug disposition in large‐molecule and small‐molecule compounds. J Clin Pharmacol. 2020;60(2):149‐163. Farrell PJ, Zopf CJ, Huang HJ, et al. Using target engagement biomarkers to predict clinical efficacy of MetAP2 inhibitors. J Pharmacol Exp Ther. 2019;371(2):299‐308. Nijhof IS, Casneuf T, van Velzen J, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016;128(7):959‐970. Saltarella I, Desantis V, Melaccio A, et al. Mechanisms of resistance to anti‐CD38 daratumumab in multiple myeloma. Cells. 2020;9(1):167. Adamia S, Ogiya D, Hatjiharissi E, et al. Identification a novel molecular mechanism underlying the anti‐CD38‐based treatment resistance in multiple myeloma patients. Blood. 2022;140:2081‐2082. Verkleij CPM, Frerichs KA, Broekmans MEC, et al. NK cell phenotype is associated with response and resistance to daratumumab in relapsed/refractory multiple myeloma. Hema. 2023;7(5):e881. Djebbari F, Poynton M, Sangha G, et al. Outcomes of anti‐CD38 isatuximab plus pomalidomide and dexamethasone in five relapsed myeloma patients with prior exposure to anti‐C38 daratumumab: case series. Hematology. 2022;27(1):204‐207. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128(1):37‐44. Mikhael J, Richter J, Vij R, et al. A dose‐finding phase 2 study of single agent isatuximab (anti‐CD38 mAb) in relapsed/refractory multiple myeloma. Leukemia. 2020;34(12):3298‐3309. Richardson PG, San Miguel JF, Moreau P, et al. Interpreting clinical trial data in multiple myeloma: translating findings to the real‐world setting. Blood Cancer J. 2018;8(11):109. |
| فهرسة مساهمة: | Keywords: Fc‐engineered; anti‐CD38; daratumumab; isatuximab; multiple myeloma; relapsed/refractory |
| تواريخ الأحداث: | Date Created: 20240712 Latest Revision: 20240712 |
| رمز التحديث: | 20240712 |
| DOI: | 10.1111/ejh.14270 |
| PMID: | 38993150 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1600-0609 |
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| DOI: | 10.1111/ejh.14270 |