Study of Elranatamab for Relapsed or Refractory Myeloma in Patients Previously Exposed to Three-drug Classes

Summary

The goal of this phase II, open-label, single-arm, multicenter study is to evaluate i) the efficacy and ii) safety of elranatamab monotherapy at the dose of 76 mg subcutaneously in participants with RRMM after at least one or two prior lines of therapy who have received prior treatment with immunomodulatory drugs, protease inhibitors, and anti-CD38 therapy and were refractory to the last line of therapy, defined as progression while receiving treatment or in the first 60 days after the last dose of treatment. Efficacy refers to the rate of Undetectable Measurable Residual Disease at 6 and 12 months as per International Myeloma Working Group (IMWG) criteria evaluated by the investigators. Safety refers to the measurement of: i) Adverse events (AEs) and serious adverse events (SAEs) according to standard clinical and laboratory tests (hematology and chemistry, physical examination, vital sign measurements, and diagnostic tests). ii) Incidence and severity of Cytokine Release Syndrome (CRS) and Immune effector cell associated neurotoxicity syndrome (ICANS) according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. iii) Incidence and severity of other neurotoxicities. iv) Incidence of cytopenias and infections The study consists of a screening/baseline period, a treatment period, and a posttreatment follow-up period. The study includes a periodic review of safety data, that will be independently analyzed by the Data Safety Independent Committee (DSMC) and will recommend how to proceed with the study.

Timeline

Start

2023-11-23

Primary completion

2025-05-30

Completion

2029-12

Publications

• Background van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021 Jan 30;397(10272):410-427. doi: 10.1016/S0140-6736(21)00135-5.
• Background Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, Delforge M, Hajek R, Schjesvold F, Cavo M, Goldschmidt H, Facon T, Einsele H, Boccadoro M, San-Miguel J, Sonneveld P, Mey U; EHA Guidelines Committee. Electronic address: [email protected]; ESMO Guidelines Committee. Electronic address: [email protected]. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2021 Mar;32(3):309-322. doi: 10.1016/j.annonc.2020.11.014. Epub 2021 Feb 3. No abstract available.
• Background Moreau P, Kumar SK, San Miguel J, Davies F, Zamagni E, Bahlis N, Ludwig H, Mikhael J, Terpos E, Schjesvold F, Martin T, Yong K, Durie BGM, Facon T, Jurczyszyn A, Sidana S, Raje N, van de Donk N, Lonial S, Cavo M, Kristinsson SY, Lentzsch S, Hajek R, Anderson KC, Joao C, Einsele H, Sonneveld P, Engelhardt M, Fonseca R, Vangsted A, Weisel K, Baz R, Hungria V, Berdeja JG, Leal da Costa F, Maiolino A, Waage A, Vesole DH, Ocio EM, Quach H, Driessen C, Blade J, Leleu X, Riva E, Bergsagel PL, Hou J, Chng WJ, Mellqvist UH, Dytfeld D, Harousseau JL, Goldschmidt H, Laubach J, Munshi NC, Gay F, Beksac M, Costa LJ, Kaiser M, Hari P, Boccadoro M, Usmani SZ, Zweegman S, Holstein S, Sezer O, Harrison S, Nahi H, Cook G, Mateos MV, Rajkumar SV, Dimopoulos MA, Richardson PG. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021 Mar;22(3):e105-e118. doi: 10.1016/S1470-2045(20)30756-7.
• Background Casanova M, Mateos MV, de Arriba F, al. e. Determination of the Value Contribution of Belantamab Mafodotin (Belamaf; BLENREP®) for the Treatment of Triple-Class Refractory Multiple Myeloma in Spain through Reflective Multi-Criteria Decision Analysis. Rev Esp Econ Salud. 2021;16(3):58-69.
• Background European Medicines Agency. NEXPOVIO. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/nexpovio-epar-product-informat ion_es.pdf . 2022.
• Background European Medicines Agency. BLENREP. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/blenrep-epar-product-informa tion_es.pdf . 2022.
• Background Yang Q, Li X, Zhang F, Yang Q, Zhou W, Liu J. Efficacy and Safety of CAR-T Therapy for Relapse or Refractory Multiple Myeloma: A systematic review and meta-analysis. Int J Med Sci. 2021 Feb 18;18(8):1786-1797. doi: 10.7150/ijms.46811. eCollection 2021.
• Background Zhang L, Shen X, Yu W, Li J, Zhang J, Zhang R, Li J, Chen L. Comprehensive meta-analysis of anti-BCMA chimeric antigen receptor T-cell therapy in relapsed or refractory multiple myeloma. Ann Med. 2021 Dec;53(1):1547-1559. doi: 10.1080/07853890.2021.1970218.
• Background Cho SF, Yeh TJ, Anderson KC, Tai YT. Bispecific antibodies in multiple myeloma treatment: A journey in progress. Front Oncol. 2022 Oct 18;12:1032775. doi: 10.3389/fonc.2022.1032775. eCollection 2022.
• Background Food and Drug Administration. FDA approves idecabtagene vicleucel for multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-idecabtagenevicleucel- multiple-myeloma . 2022.
• Background European Medicines Agency. Abecma. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/abecma-epar-product-informati on_en.pdf . 2022.
• Background Food and Drug Administration. FDA approves ciltacabtagene autoleucel for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ciltacabtageneautoleucel- relapsed-or-refractory-multiple-myeloma . 2022.
• Background European Medicines Agency. CARVYKTI. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/carvykti-epar-product-informatio n_en.pdf . 2022.
• Background Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, Moreau P, Yakoub-Agha I, Delforge M, Cavo M, Einsele H, Goldschmidt H, Weisel K, Rambaldi A, Reece D, Petrocca F, Massaro M, Connarn JN, Kaiser S, Patel P, Huang L, Campbell TB, Hege K, San-Miguel J. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 Feb 25;384(8):705-716. doi: 10.1056/NEJMoa2024850.
• Background Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, Deol A, Munshi NC, O'Donnell E, Avigan D, Singh I, Zudaire E, Yeh TM, Allred AJ, Olyslager Y, Banerjee A, Jackson CC, Goldberg JD, Schecter JM, Deraedt W, Zhuang SH, Infante J, Geng D, Wu X, Carrasco-Alfonso MJ, Akram M, Hossain F, Rizvi S, Fan F, Lin Y, Martin T, Jagannath S. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021 Jul 24;398(10297):314-324. doi: 10.1016/S0140-6736(21)00933-8. Epub 2021 Jun 24.
• Background Food and Drug Administration. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cq yv-relapsed-or-refractory-multiple-myeloma . 2022.
• Background European Medicines Agency. TECVAYLI. Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tecvayli-epar-product-informatio n_en.pdf . 2022.
• Background Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martinez-Lopez J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.
• Background Lassiter G, Bergeron C, Guedry R, Cucarola J, Kaye AM, Cornett EM, Kaye AD, Varrassi G, Viswanath O, Urits I. Belantamab Mafodotin to Treat Multiple Myeloma: A Comprehensive Review of Disease, Drug Efficacy and Side Effects. Curr Oncol. 2021 Jan 21;28(1):640-660. doi: 10.3390/curroncol28010063.
• Background Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187-99. doi: 10.2217/imt.15.77. Epub 2015 Sep 15.
• Background Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, Podar K, Hideshima T, Chauhan D, Raje N, Schlossman R, Richardson P, Munshi NC, Anderson KC. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 2006 Jul 1;66(13):6675-82. doi: 10.1158/0008-5472.CAN-06-0190.
• Background Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, Yellin O, Nichols CM, Dreyer MP, Ahles CP, Robinson A, Madden E, Waterman GN, Swift RA, Bonavida B, Boccia R, Vescio RA, Crowley J, Chen H, Berenson JR. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012 Sep;158(6):727-38. doi: 10.1111/j.1365-2141.2012.09241.x. Epub 2012 Jul 18.
• Background Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004 Jan 15;103(2):689-94. doi: 10.1182/blood-2003-06-2043. Epub 2003 Sep 25.
• Background Shah N, Chari A, Scott E, Mezzi K, Usmani SZ. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. Leukemia. 2020 Apr;34(4):985-1005. doi: 10.1038/s41375-020-0734-z. Epub 2020 Feb 13.
• Background Lesokhin AM, Raje N, Gasparetto CJ, et al. A Phase I, Open-Label Study to Evaluate the Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity of PF-06863135, a B-Cell Maturation Antigen/CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Advanced Multiple Myeloma. Blood. 2018;132(Supplement 1):3229-3229.
• Background Panowski SH, Kuo TC, Zhang Y, Chen A, Geng T, Aschenbrenner L, Kamperschroer C, Pascua E, Chen W, Delaria K, Farias S, Bateman M, Dushin RG, Chin SM, Van Blarcom TJ, Yeung YA, Lindquist KC, Chunyk AG, Kuang B, Han B, Mirsky M, Pardo I, Buetow B, Martin TG, Wolf JL, Shelton D, Rajpal A, Strop P, Chaparro-Riggers J, Sasu BJ. Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. Mol Cancer Ther. 2019 Nov;18(11):2008-2020. doi: 10.1158/1535-7163.MCT-19-0007. Epub 2019 Aug 21.
• Background Karwacz K, Hooper AT, Chang C-PB, et al. Abstract 4557: BCMA-CD3 bispecific antibody PF-06863135: Preclinical rationale for therapeutic combinations. Immunology. 2020;80:4557-4557.
• Background Sebag M, Raje NS, Bahlis NJ, et al. Elranatamab (PF-06863135), a B-Cell Maturation Antigen (BCMA) Targeted CD3-Engaging Bispecific Molecule, for Patients with Relapsed or Refractory Multiple Myeloma: Results from Magnetismm-1. Blood. 2021;138(Supplement 1):895-895
• Background Raje N, Bahlis NJ, Costello C, al. e. Elranatamab, a BCMA Targeted T-Cell Engaging Bispecific Antibody, Induces Durable Clinical and Molecular Responses for Patients with Relapsed or Refractory Multiple Myeloma. Blood. 2022;140:388-390.
• Background Lesokhin AM, Arnulf B, Niesvizky R, et al. Initial safety results for MagnetisMM-3: A phase 2 trial of elranatamab, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients (pts) with relapsed/refractory (R/R) multiple myeloma (MM). Journal of Clinical Oncology. 2022;40(16_suppl):8006-8006.
• Background Bahlis NJ, Tomasson MH, Mohty M, al. e. Efficacy and Safety of Elranatamab in Patients with Relapsed/Refractory Multiple Myeloma Naïve to B-Cell Maturation Antigen (BCMA)-Directed Therapies: Results from Cohort a of the Magnetismm-3 Study. Blood. 2022;140:391-393.
• Background Pfizer. Pfizer Presents Updated Favorable Elranatamab Data from Pivotal Phase 2 MagnetisMM-3 Trial. Press release available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-updated-favora ble-elranatamab-data-pivotal . 2022.
• Background Pfizer. PF-06863135 As Single Agent And In Combination With Immunomodulatory Agents In Relapse/Refractory Multiple Myeloma. ClinicalTrials.gov Identifier: NCT03269136. Updated July 11, 2022. Accessed September 17, 2022. https://clinicaltrials.gov/ct2/show/NCT03269136 . 2022.
• Background Pfizer. Pfizer Presents First Data from Planned Interim Analysis of Pivotal Phase 2 MagnetisMM-3 Trial of BCMA-CD3 Bispecific Antibody Elranatamab Under Investigation for Relapsed/Refractory Multiple Myeloma. Press release available at: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-presents-first-data-plann ed-interim-analysis-pivotal . 2022.
• Background Elmeliegy M, Viqueira A, Erik Vandendries E, al. e. Dose Optimization to Mitigate the Risk of CRS with Elranatamab in Multiple Myeloma. Presented at the: 64th ASH Annual Meeting & Exposition, New Orleans, December 10-13, 2022. Available at: https://ash.confex.com/ash/2022/webprogram/Paper169971.html . 2022.
• Background Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, Sherrington P, Samur MK, Georgieva A, Anderson KC, Gregory WM. Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis. JAMA Oncol. 2017 Jan 1;3(1):28-35. doi: 10.1001/jamaoncol.2016.3160.
• Background Lahuerta JJ, Paiva B, Vidriales MB, Cordon L, Cedena MT, Puig N, Martinez-Lopez J, Rosinol L, Gutierrez NC, Martin-Ramos ML, Oriol A, Teruel AI, Echeveste MA, de Paz R, de Arriba F, Hernandez MT, Palomera L, Martinez R, Martin A, Alegre A, De la Rubia J, Orfao A, Mateos MV, Blade J, San-Miguel JF; GEM (Grupo Espanol de Mieloma)/PETHEMA (Programa para el Estudio de la Terapeutica en Hemopatias Malignas) Cooperative Study Group. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials. J Clin Oncol. 2017 Sep 1;35(25):2900-2910. doi: 10.1200/JCO.2016.69.2517. Epub 2017 May 12.
• Background Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016 Nov 15;316(19):2025-2035. doi: 10.1001/jama.2016.9185.
• Background Kumar SK, Callander NS, Adekola K, Anderson L, Baljevic M, Campagnaro E, Castillo JJ, Chandler JC, Costello C, Efebera Y, Faiman M, Garfall A, Godby K, Hillengass J, Holmberg L, Htut M, Huff CA, Kang Y, Hultcrantz M, Larson S, Liedtke M, Martin T, Omel J, Shain K, Sborov D, Stockerl-Goldstein K, Weber D, Keller J, Kumar R. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020 Dec 2;18(12):1685-1717. doi: 10.6004/jnccn.2020.0057.
• Background Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, Krishnan A, Hari P, Ludwig H, O'Donnell E, Yee A, Kaufman JL, Cohen AD, Garderet L, Wechalekar AF, Terpos E, Khatry N, Niesvizky R, Yi Q, Joshua DE, Saikia T, Leung N, Engelhardt M, Mothy M, Branagan A, Chari A, Reiman AJ, Lipe B, Richter J, Rajkumar SV, Miguel JS, Anderson KC, Stadtmauer EA, Prabhala RH, McCarthy PL, Munshi NC. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022 Feb;9(2):e143-e161. doi: 10.1016/S2352-3026(21)00283-0.
• Background Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
• Background Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, Terpos E, Munshi N, Palumbo A, Rajkumar SV, Harousseau JL, Moreau P, Avet-Loiseau H, Lee JH, Cavo M, Merlini G, Voorhees P, Chng WJ, Mazumder A, Usmani S, Einsele H, Comenzo R, Orlowski R, Vesole D, Lahuerta JJ, Niesvizky R, Siegel D, Mateos MV, Dimopoulos M, Lonial S, Jagannath S, Blade J, Miguel JS, Morgan G, Anderson KC, Durie BG, Sonneveld P. Management of treatment-emergent peripheral neuropathy in multiple myeloma. Leukemia. 2012 Apr;26(4):595-608. doi: 10.1038/leu.2011.346. Epub 2011 Dec 23.
• Background Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, Kronke J, Facon T, Salnikov AV, Lesley R, Beutner K, Kalabus J, Rasmussen E, Riemann K, Minella AC, Munzert G, Einsele H. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020 Mar 10;38(8):775-783. doi: 10.1200/JCO.19.02657. Epub 2020 Jan 2.

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Indications