PHASE 3, RANDOMIZED STUDY OF TALQUETAMAB (TAL) PLUS DARATUMUMAB (DARA) ± POMALIDOMIDE (POM) VS DARA PLUS POM AND DEXAMETHASONE (DPD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): MONUMENTAL-3
40 affiliations
- 1Atrium Health/Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC, United States
- 2Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, United States
- 3Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain
- 4Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing, China
- 5Hospital Clínico Universitario de Salamanca, Servicio de Salud de Castilla y León (SACYL), Salamanca, Castile and León, Spain
- 6Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- 7Hematology Clinic, University Hospital Hôtel-Dieu, Nantes, France
- 8Tel-Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel; Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel
- 9Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
- 10Department of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic; Department of Hematooncology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
- 11MD Anderson Cancer Center, University of Texas, Houston, TX, United States
- 12Chaim Sheba Medical Center, Ramat-Gan, Israel; Sackler Faculty of Medical and Health Sciences, Tel Aviv University, Israel
- 13Division of Hematology and Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
- 14Department of Hematology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, 200434 Shanghai, China
- 15Clínica Médica São Germano, São Paulo, SP, Brazil
- 16Ankara University Faculty of Medicine, Department of Hematology and Oncology, Ankara University, Ankara, Türkiye
- 17Liga Paranaense de Combate ao Câncer (LPCC), Curitiba, PA, Brazil
- 18Hematology, University Hospital Hradec Kralove, Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
- 19Medipol Mega University Hospital, Bağcılar, İstanbul, Türkiye
- 20Ondokuz Mayıs University, Samsun, Türkiye
- 21Seoul National University Hospital, Seoul National University, Jongno-gu, Seoul, South Korea
- 22University of Minnesota, Minneapolis, MN, United States
- 23A.C. Camargo Cancer Center, São Paulo, SP, Brazil
- 24Novant Health Cancer Institute, Winston-Salem, NC, United States
- 25Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China
- 26National Taiwan University Hospital, National Taiwan University College of Medicine, Zhongzheng District, Taipei, Taiwan
- 27Department of Cancer Prevention, Medical University of Silesia, Katowice, Poland
- 28Medical University of Gdańsk, Department of Hematology and Transplantology, University Clinical Center Gdańsk, Department of Hematology and Transplantology, Gdańsk, Poland
- 29Fred Hutchinson Cancer Center, Seattle, United States
- 30University of Michigan Health, Ann Arbor, United States
- 31Hospital Universitario 12 de Octubre, imas12/Complutense University of Madrid/CNIO/Madrid, Spain
- 32Holy Cross Cancer Center, Department of Hematology and Bone Marrow Transplantation, Kielce, Poland
- 33Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), Koto-ku, Tokyo, Japan
- 34The University of Osaka Graduate School of Medicine, Suita, Japan
- 35Hospital Universitari Germans Trias i Pujol (HUGTiP), Institut Català de la Salut (ICS), Badalona, Barcelona, Spain
- 36l’Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
- 37Internal Medicine V, Hematology, Oncology and Rheumatology, GMMG Study Group, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany
- 38The Institute of Cancer Research, London, UK, and The Royal Marsden NHS Foundation Trust, London, United Kingdom
- 39Université de Toulouse, Centre Hospitalier Universitaire de Toulouse, Service Hématologie, IUCT Oncopole, Toulouse, France
- 40University of Bologna, Bologna, Italy
Abstract
Background: Tal (anti-GPRC5D bispecific antibody) has shown deep, durable responses in late-line RRMM with a favorable infection profile. Its B-cell–sparing mechanism supports combination with Dara and Pom, potentially enhancing efficacy in earlier lines. We report efficacy and safety from a pre-planned interim analysis of MonumenTAL-3 (NCT05455320) comparing Tal-DP and Tal-D vs DPd in RRMM after ≥1 prior LOT. Methods: Phase 3 study randomizing pts with RRMM after ≥1 prior LOT including lenalidomide (Len) and a proteasome inhibitor 1:1:1 to Tal-DP, Tal-D, or DPd. Primary endpoint was IRC-assessed PFS for Tal-DP vs DPd and Tal-D vs DPd. Secondary endpoints included response, ≥CR, MRD-negative ≥CR (10−5; NGS), OS, and safety. Results: Overall, 864 pts were randomized (Tal-DP, N=287; Tal-D, N=287; DPd, N=290). Baseline characteristics were balanced across arms. Median age was 64.0 yrs (range 30–88), median prior LOT was 2 (range 1–8); 11.8% were anti-CD38 (nearly all Dara) exposed; 85.1% and 93.4% were refractory to Len or last LOT, respectively; 30.9% had high risk cytogenetics. At 24.6 mo median follow-up, Tal-DP and Tal-D significantly improved PFS vs DPd (HRs 0.28 [0.20–0.40], P<0.0001 and 0.33 [0.24–0.46], P<0.0001. 24-mo PFS rates favored Tal-DP (81.3% [75.8–85.7]) and Tal-D (77.6% [71.7–82.5]) vs DPd (51.2% [44.8–57.1]) PFS benefit was consistent across clinically relevant subgroups. ORRs (88.2%, 88.5%, 77.6%) ≥CR rates (71.1%, 69.0%, 34.5%) and MRD-negative ≥CR rates (52.3%, 46.3%, 15.9%) were significantly higher for Tal-DP and Tal-D vs DPd, respectively. OS HRs (95% CI) vs DPd were 0.47 (0.30–0.73; P=0.0006) for Tal-DP and 0.51 (0.33–0.78; P=0.0015) for Tal-D. At data cutoff, 70.3% (Tal-DP), 69.7% (Tal-D) and 47.3% (DPd) of pts remained on study tx. AEs were manageable and consistent with expectations for each agent; overall AE rates (gr 3-4, gr 5) Tal-DP (96.7%, 1.8%), Tal-D (78.8%, 4.0%), DPd (95.8%, 4.6%). AEs leading to discontinuation (d/c) of all study tx occurred in 10.5% (Tal-DP), 8.0% (Tal-D), and 6.7% (DPd). Rates of cytopenias (any gr, gr 3-4) were: Tal-DP (91.7%, 87.7%), Tal-D (68.2%, 51.8%) and DPd (91.9%, 89.0%). Infection rates (any gr, gr 3-4, gr 5) were: Tal-DP (87.3%, 37.0%, 0.7%) Tal-D (84.3%, 27.7%, 1.5%), and DPd (83.0%, 41.0%, 1.8%). With Tal-DP and Tal-D, respectively, CRS (any gr: 67.8%; 58.4%) and ICANS (any gr: 2.9%; 1.8%) were mostly gr 1-2. Any gr GPRC5D-related AEs with Tal-DP, Tal-D and DPd, respectively, included taste changes (72.8%; 74.8%; 3.9%) and decreased weight (45.7%; 38.3%; 7.4%); most events were gr 1-2 and did not lead to Tal d/c. Ataxia/balance disorders (gr 1-2, gr 3) with Tal-DP (11.6%, 2.9%), Tal-D (10.2%, 2.2%) and DPd (0.4%, 0%) were primarily low gr (none gr ≥4); events led to Tal d/c in 4.7% (Tal-DP) and 2.2% (Tal-D). Conclusions: Tal-DP and Tal-D demonstrated a significant and profound PFS benefit vs DPd, clinically meaningful OS improvements and gr ≥3 infection rates similar to or lower than DPd. Tal was combinable, with low rates of tx d/c. Efficacy appeared numerically better with Tal-DP vs Tal-D but with a higher gr 3-4 cytopenia rate, as expected with Pom. Tal-D with or without Pom represents a new standard of care for RRMM as early as 2L across all practice settings.
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BibTeX
@article{voorhees2026phase,
title = {{PHASE 3, RANDOMIZED STUDY OF TALQUETAMAB (TAL) PLUS DARATUMUMAB (DARA) ± POMALIDOMIDE (POM) VS DARA PLUS POM AND DEXAMETHASONE (DPD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): MONUMENTAL-3}},
author = {Peter VOORHEES and Roberto MINA and Paula RODRÍGUEZ OTERO and Wenming CHEN and María Victoria MATEOS and Jian LI and Philippe MOREAU and Yael COHEN and Chang KI MIN and Roman HAJEK and Christine YE and Hila MAGEN and Sam RUBINSTEIN and Weijun FU and Vania HUNGRIA and Guldane CENGIZ SEVAL and Joao Samuel SAMUEL FARIAS and Jakub RADOCHA and Senem MARAL and Mehmet TURGUT and Youngil KOH and Daniel O'LEARY and Jayr SCHMIDT FILHO and Raymond THERTULIEN and Gang AN and Shang YI HUANG and Sebastian GROSICKI and Agata TYCZYNSKA and Rahul BANERJEE and Matthew PIANKO and Joaquín MARTÍNEZ-LÓPEZ and Pawel STECKIEWICZ and Dai Maruyamadai MARUYAMA and Kentaro FUKUSHIMA and Albert ORIOL and Jordi LOPEZ PARDO and Hartmut GOLDSCHMIDT and Charlotte PAWLYN and Aurore PERROT and Elena ZAMAGNI and Meletios Athanasios DIMOPOULOS and Leo RASCHE and Jaszianne TOLBERT and Jaszianne TOLBERT and William TERRY and Christelle COURTOUX and Xiao LIU and Sandra Y VASEY and Kaitlyn CONNORS and Maria Cristina FESTA and Christoph HEUCK and Angélique LANGLOIS and Lisa O'ROURKE and Jiangxiu ZHOU and Xiang QIN and Jiashen LU and Jue GONG and Diego VIEYRA and Meral BEKSAC},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107913},
url = {https://doi.org/10.1016/j.htct.2026.107913},
note = {CC BY},
}
RIS
TY - JOUR
TI - PHASE 3, RANDOMIZED STUDY OF TALQUETAMAB (TAL) PLUS DARATUMUMAB (DARA) ± POMALIDOMIDE (POM) VS DARA PLUS POM AND DEXAMETHASONE (DPD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): MONUMENTAL-3
AU - Peter VOORHEES
AU - Roberto MINA
AU - Paula RODRÍGUEZ OTERO
AU - Wenming CHEN
AU - María Victoria MATEOS
AU - Jian LI
AU - Philippe MOREAU
AU - Yael COHEN
AU - Chang KI MIN
AU - Roman HAJEK
AU - Christine YE
AU - Hila MAGEN
AU - Sam RUBINSTEIN
AU - Weijun FU
AU - Vania HUNGRIA
AU - Guldane CENGIZ SEVAL
AU - Joao Samuel SAMUEL FARIAS
AU - Jakub RADOCHA
AU - Senem MARAL
AU - Mehmet TURGUT
AU - Youngil KOH
AU - Daniel O'LEARY
AU - Jayr SCHMIDT FILHO
AU - Raymond THERTULIEN
AU - Gang AN
AU - Shang YI HUANG
AU - Sebastian GROSICKI
AU - Agata TYCZYNSKA
AU - Rahul BANERJEE
AU - Matthew PIANKO
AU - Joaquín MARTÍNEZ-LÓPEZ
AU - Pawel STECKIEWICZ
AU - Dai Maruyamadai MARUYAMA
AU - Kentaro FUKUSHIMA
AU - Albert ORIOL
AU - Jordi LOPEZ PARDO
AU - Hartmut GOLDSCHMIDT
AU - Charlotte PAWLYN
AU - Aurore PERROT
AU - Elena ZAMAGNI
AU - Meletios Athanasios DIMOPOULOS
AU - Leo RASCHE
AU - Jaszianne TOLBERT
AU - Jaszianne TOLBERT
AU - William TERRY
AU - Christelle COURTOUX
AU - Xiao LIU
AU - Sandra Y VASEY
AU - Kaitlyn CONNORS
AU - Maria Cristina FESTA
AU - Christoph HEUCK
AU - Angélique LANGLOIS
AU - Lisa O'ROURKE
AU - Jiangxiu ZHOU
AU - Xiang QIN
AU - Jiashen LU
AU - Jue GONG
AU - Diego VIEYRA
AU - Meral BEKSAC
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107913
UR - https://doi.org/10.1016/j.htct.2026.107913
AB - Background: Tal (anti-GPRC5D bispecific antibody) has shown deep, durable responses in late-line RRMM with a favorable infection profile. Its B-cell–sparing mechanism supports combination with Dara and Pom, potentially enhancing efficacy in earlier lines. We report efficacy and safety from a pre-planned interim analysis of MonumenTAL-3 (NCT05455320) comparing Tal-DP and Tal-D vs DPd in RRMM after ≥1 prior LOT. Methods: Phase 3 study randomizing pts with RRMM after ≥1 prior LOT including lenalidomide (Len) and a proteasome inhibitor 1:1:1 to Tal-DP, Tal-D, or DPd. Primary endpoint was IRC-assessed PFS for Tal-DP vs DPd and Tal-D vs DPd. Secondary endpoints included response, ≥CR, MRD-negative ≥CR (10−5; NGS), OS, and safety. Results: Overall, 864 pts were randomized (Tal-DP, N=287; Tal-D, N=287; DPd, N=290). Baseline characteristics were balanced across arms. Median age was 64.0 yrs (range 30–88), median prior LOT was 2 (range 1–8); 11.8% were anti-CD38 (nearly all Dara) exposed; 85.1% and 93.4% were refractory to Len or last LOT, respectively; 30.9% had high risk cytogenetics. At 24.6 mo median follow-up, Tal-DP and Tal-D significantly improved PFS vs DPd (HRs 0.28 [0.20–0.40], P<0.0001 and 0.33 [0.24–0.46], P<0.0001. 24-mo PFS rates favored Tal-DP (81.3% [75.8–85.7]) and Tal-D (77.6% [71.7–82.5]) vs DPd (51.2% [44.8–57.1]) PFS benefit was consistent across clinically relevant subgroups. ORRs (88.2%, 88.5%, 77.6%) ≥CR rates (71.1%, 69.0%, 34.5%) and MRD-negative ≥CR rates (52.3%, 46.3%, 15.9%) were significantly higher for Tal-DP and Tal-D vs DPd, respectively. OS HRs (95% CI) vs DPd were 0.47 (0.30–0.73; P=0.0006) for Tal-DP and 0.51 (0.33–0.78; P=0.0015) for Tal-D. At data cutoff, 70.3% (Tal-DP), 69.7% (Tal-D) and 47.3% (DPd) of pts remained on study tx. AEs were manageable and consistent with expectations for each agent; overall AE rates (gr 3-4, gr 5) Tal-DP (96.7%, 1.8%), Tal-D (78.8%, 4.0%), DPd (95.8%, 4.6%). AEs leading to discontinuation (d/c) of all study tx occurred in 10.5% (Tal-DP), 8.0% (Tal-D), and 6.7% (DPd). Rates of cytopenias (any gr, gr 3-4) were: Tal-DP (91.7%, 87.7%), Tal-D (68.2%, 51.8%) and DPd (91.9%, 89.0%). Infection rates (any gr, gr 3-4, gr 5) were: Tal-DP (87.3%, 37.0%, 0.7%) Tal-D (84.3%, 27.7%, 1.5%), and DPd (83.0%, 41.0%, 1.8%). With Tal-DP and Tal-D, respectively, CRS (any gr: 67.8%; 58.4%) and ICANS (any gr: 2.9%; 1.8%) were mostly gr 1-2. Any gr GPRC5D-related AEs with Tal-DP, Tal-D and DPd, respectively, included taste changes (72.8%; 74.8%; 3.9%) and decreased weight (45.7%; 38.3%; 7.4%); most events were gr 1-2 and did not lead to Tal d/c. Ataxia/balance disorders (gr 1-2, gr 3) with Tal-DP (11.6%, 2.9%), Tal-D (10.2%, 2.2%) and DPd (0.4%, 0%) were primarily low gr (none gr ≥4); events led to Tal d/c in 4.7% (Tal-DP) and 2.2% (Tal-D). Conclusions: Tal-DP and Tal-D demonstrated a significant and profound PFS benefit vs DPd, clinically meaningful OS improvements and gr ≥3 infection rates similar to or lower than DPd. Tal was combinable, with low rates of tx d/c. Efficacy appeared numerically better with Tal-DP vs Tal-D but with a higher gr 3-4 cytopenia rate, as expected with Pom. Tal-D with or without Pom represents a new standard of care for RRMM as early as 2L across all practice settings.
SN - 2531-1379
SN - 2531-1387
ER -