A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

Official title

A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

Overview

The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

Interventions

• Drug Talquetamab
  Talquetamab will be administered SC until disease progression.

Primary outcome measures

• Overall Response Rate (ORR) [Time frame: Up to 2 years and 10 months]

Secondary outcome measures (12)

• Duration of Response (DOR) [Time frame: Up to 2 years and 10 months]
• Very Good Partial Response (VGPR) or Better Rate [Time frame: Up to 2 years and 10 months]
• Complete Response (CR) or Better Rate [Time frame: Up to 2 years and 10 months]
• Stringent Complete Response (sCR) Rate [Time frame: Up to 2 years and 10 months]
• Time to Response (TTR) [Time frame: Up to 2 years and 10 months]
• Progression-Free Survival (PFS) [Time frame: Up to 2 years and 10 months]
• Overall Survival (OS) [Time frame: Up to 2 years and 10 months]
• Minimal Residual Disease (MRD) Negative Rate [Time frame: Up to 2 years and 10 months]
• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Time frame: Up to 2 years and 10 months]
• Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [Time frame: Up to 2 years and 10 months]
• Number of Participants with AEs by Severity [Time frame: Up to 2 years and 10 months]
• Number of Participants with Abnormalities in Clinical Laboratory Values [Time frame: Up to 2 years and 10 months]

Eligibility criteria

Inclusion criteria

• Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
• Part 3: Measurable disease cohort A, cohort B, cohort C and cohort D: multiple myeloma must be measurable by central laboratory assessment; Cohort E: Multiple myeloma must be measurable by local laboratory assessment
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin \[hCG\]) or urine
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion criteria

• Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B, Cohort D and Cohort E: T cell redirection therapy within 3 months
• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
• Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• Stroke or seizure within 6 months prior to signing the informed consent form (ICF)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• University of Alabama Birmingham — Birmingham
• University of Arkansas for Medical Sciences — Little Rock
• City of Hope — Duarte
• Memorial Healthcare System — Hollywood
• Emory University Winship Cancer Institute — Atlanta
• University of Chicago — Chicago
• Norton Cancer Institute — Louisville
• University of Michigan Health System — Ann Arbor
• … and 6 more centers

Japan · 13 centers

• Kameda Medical Center — Chiba
• Fukuoka University Hospital — Fukuoka
• Ogaki Municipal Hospital — Gifu
• Teine Keijinkai Hospital — Hokkaido
• Kobe City Medical Center General Hospital — Kobe
• Dokkyo Medical University Saitama Medical Center — Koshigaya
• Kumamoto University Hospital — Kumamoto
• Kurashiki Central Hospital — Kurashiki
• … and 5 more centers

Spain · 11 centers

• Hosp. Univ. Germans Trias I Pujol — Badalona
• Hosp Univ Vall D Hebron — Barcelona
• Inst. Cat. Doncologia-H Duran I Reynals — Barcelona
• Hosp Univ Fund Jimenez Diaz — Madrid
• Hosp. Univ. 12 de Octubre — Madrid
• Hosp. Univ. Virgen de La Arrixaca — Murcia
• Clinica Univ. de Navarra — Pamplona
• Hosp. Quiron Madrid Pozuelo — Pozuelo de Alarcón
• … and 3 more centers

China · 8 centers

• Peking University Third Hospital — Beijing
• Sun Yat Sen University Cancer Center — Guangzhou
• The 1st Affiliated Hospital Of Medical College Zhejiang University 1 — Hangzhou
• The 1St Affiliated Hospital of Medical College Zhejiang University — Hangzhou
• First Affiliated Hospital SooChow University — Suzhou
• Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science — Tianjin
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an
• The First Affiliated Hospital of Xian Jiaotong University — Xi'an

France · 6 centers

• CHU Henri Mondor — Créteil
• Hospices Civils de Lyon HCL — Lyon
• CHU de Montpellier Hopital Saint Eloi — Montpellier
• C.H.U. Hotel Dieu - France — Nantes
• CHU de Bordeaux - Hospital Haut-Leveque — Pessac
• Pôle IUC Oncopole CHU — Toulouse

South Korea · 6 centers

• Chonnam National University Hwasun Hospital — Jeollanam-do
• Seoul National University Hospital — Seoul
• Severance Hospital Yonsei University Health System — Seoul
• Asan Medical Center — Seoul
• Samsung Medical Center — Seoul
• The Catholic University of Korea Seoul St Marys Hospital — Seoul

Israel · 5 centers

• Rambam Medical Center — Haifa
• Carmel Medical Center — Haifa
• Hadassah Medical Center — Jerusalem
• Sheba Medical Center — Ramat Gan
• Tel Aviv Sourasky Medical Center — Tel Aviv

Poland · 5 centers

• Uniwersyteckie Centrum Kliniczne — Gdansk
• Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w — Gliwice
• Uniwersytecki Szpital Kliniczny w Poznaniu — Poznan
• Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy — Warsaw
• Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu — Wroclaw

Belgium · 4 centers

• UZ Antwerpen — Edegem
• UZ Leuven — Leuven
• CHU de Liège - Domaine Universitaire du Sart Tilman — Liège
• UCL - Saint Luc — Woluwe-Saint-Lambert

Germany · 4 centers

• Charite Campus Benjamin Franklin — Berlin
• Universitaetsklinikum Heidelberg — Heidelberg
• Universitaetsklinikum Muenster — Münster
• Universitatsklinikum Wurzburg — Würzburg

Netherlands · 2 centers

• VU Medisch Centrum — Amsterdam
• UMCU — Utrecht

Publications

• Schinke C, Touzeau C, Oriol A, Mateos MV, Stevens D, Rasche L, Moreau P, San-Miguel J, Rodriguez-Otero P, Kato K, Bathija S, Katz EG, Masterson T, Tomlinson C, Chari A. A plain language summary describing how talquetamab affects the way people with multiple myeloma feel and function in the MonumenTAL-1 study. Future Oncol. 2026 Jun;22(14):1651-1668. doi: 10.1080/14796694.2026.2669331. Epub 2026 Ju PMID 42299486
• Ito S, Kuroda Y, Sunami K, Matsue K, Imada K, Tamura H, Fujikawa E, Yamazaki H, Takamoto M, Pei L, Qin X, Masterson TJ, Campagna M, Vreys V, Lau BW, Takamatsu Y. Talquetamab in Japanese patients with relapsed/refractory multiple myeloma in the MonumenTAL-1 study. Int J Hematol. 2026 Apr;123(4):580-592. doi: 10.1007/s12185-025-04134-6. Epub 2025 Dec 17. PMID 41405810
• Einsele H, Moreau P, Bahlis N, Bhutani M, Vincent L, Karlin L, Perrot A, Goldschmidt H, van de Donk NWCJ, Ocio EM, Martinez Lopez J, Rodriguez-Otero P, Dytfeld D, Jakubowiak A, Schinke C, Besemer B, Anguille S, Manier S, Rasche L, Teipel R, Scheid C, Pawlyn C, Cavo M, Diels J, Ghilotti F, Lau BW, Renaud T, Orel O, Ong F, Ramos DF, Ammann E, Parekh T, Albrecht C, Weisel K, Mateos MV. Comparative Ef PMID 41313549
• van de Donk NWCJ, Chari A, Martin T, Krishnan A, Rasche L, Ye JC, Popat R, Lipe B, Rodriguez C, Schinke C, Skerget S, Vishwamitra D, Verona R, Gong J, Singh I, Campagna M, Masterson T, Hilder B, Tolbert J, Renaud T, Smit MD, Heuck C, Mateos MV. Characterization and Management of Cytokine Release Syndrome From the MonumenTAL-1 Study of Talquetamab in Patients With Relapsed/Refractory Multiple Myelo PMID 41036677
• Schinke C, Rodriguez-Otero P, van de Donk NWCJ, Lipe B, Lavi N, Rasche L, Parekh S, Van Oekelen O, Vishwamitra D, Skerget S, Cortes-Selva D, Verona R, Hilder B, Masterson T, Campagna M, Khedkar S, Renaud T, Tolbert J, Kane C, Gray KS, Saber I, Heuck C, Chari A. Infections and parameters of humoral immunity with talquetamab in relapsed/refractory multiple myeloma in MonumenTAL-1. Blood Adv. 2025 No PMID 40864183
• Schinke C, Touzeau C, Oriol A, Mateos MV, Stevens D, Rasche L, Qin X, Kato K, Bathija S, Katz EG, Gries KS, Campagna M, Masterson T, Hilder BW, Tolbert J, Renaud T, Heuck C, Tomlinson C, Moreau P, San-Miguel J, Rodriguez-Otero P, Chari A. Talquetamab improves patient-reported symptoms and health-related quality of life in relapsed or refractory multiple myeloma: Results from the phase 1/2 MonumenT PMID 40631904
• Chari A, Touzeau C, Schinke C, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodriguez-Otero P, Morillo D, Martinez-Chamorro C, Mateos MV, Costa LJ, Caers J, Rasche L, Krishnan A, Ye JC, Karlin L, Lipe B, Vishwamitra D, Skerget S, Verona R, Ma X, Qin X, Ludlage H, Campagna M, Masterson T, Hilder B, Tolbert J, Renaud T, Goldberg JD, Kane C, Heuck C, San-Miguel J, Moreau P. Safety and activity PMID 40090350
• Catamero D, Ray C, Purcell K, Leahey S, Esler E, Rogers S, Hefner K, O'Rourke L, Gray K, Tolbert J, Renaud T, Patel S, Hannemann L, Shenoy S. Nursing Considerations for the Clinical Management of Adverse Events Associated with Talquetamab in Patients with Relapsed or Refractory Multiple Myeloma. Semin Oncol Nurs. 2024 Oct;40(5):151712. doi: 10.1016/j.soncn.2024.151712. Epub 2024 Aug 17. PMID 39155155

Identifiers

NCT: NCT04634552 · CR108920 · TALMMY1001-PT3 · 2017-002400-26 · 2023-504581-29-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗