Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)

A Phase 1, 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

The purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).

Study Overview

• Status: Active, not recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Talquetamab

Detailed Description

The study will be conducted in 2 parts: dose escalation and dose expansion. The study will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of Talquetamab administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as the last study assessment for the last participant in the study. Study record NCT04634552 is Phase 2 part of this study and study record NCT03399799 is Phase 1 part of this study.

• Study Type: Interventional
• Enrollment (Actual): 279
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • UMCU
• Spain
  • Badalona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Madrid, Spain, 28040
    • Hosp Univ Fund Jimenez Diaz
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcón, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Part 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• 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 [beta-hCG]) or urine
• Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

• Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of Talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (example, coronavirus disease [COVID]-19) by local health authorities are allowed
• 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 greater than or equal to ( >=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose of study drug
• Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation (Talquetamab) - Intravenous (IV); Participants will receive IV infusion of Talquetamab at minimum anticipated biologic effect level (MABEL)-based starting dose until the completion of the end of treatment visit. Subsequent dose levels will be selected based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and preliminary antitumor activity data. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the long-term extension (LTE) and will continue to receive study treatment.	Drug: Talquetamab; Participants will receive IV infusion or SC injection of Talquetamab.
Experimental: Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC); Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s). All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.	Drug: Talquetamab; Participants will receive IV infusion or SC injection of Talquetamab.
Experimental: Part 2: Dose Expansion (Talquetamab); Participants will receive IV infusion or SC injection of Talquetamab at each putative recommended Phase 2 dose(s) (RP2D[s]) as determined in Part 1. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.	Drug: Talquetamab; Participants will receive IV infusion or SC injection of Talquetamab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Dose-limiting Toxicity (DLT)	The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non-hematological toxicity of Grade 3 or higher.	Up to Day 28
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	From signing of Informed Consent Form (ICF) up to follow up (until 100 days after the last dose of study drug or until the start of subsequent anticancer therapy, if earlier [approximately 2.10 years])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and Part 2: Biomarker Assessment	Serum cytokine concentrations will be measured pre- and post-infusion of Talquetamab for biomarker assessment.	Up to Cycle 7 Day 1 (each cycle of 21-days)
Part 2: Overall Response Rate (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.	Approximately 2.10 years
Part 2: Clinical Benefit Rate (CBR)	CBR is defined as the proportion of participants who have a minimal response (MR) or better according to the IMWG criteria.	Approximately 2.10 years
Part 2: Duration of Response (DOR)	DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of PD, per IMWG criteria.	From the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) (approximately 2.10 years)
Part 2: Time to Response (TTR)	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.	From the date of first dose of study drug to the date of initial documentation of a response (approximately 2.10 years)
Part 2: Progression-Free Survival (PFS)	PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.	Every 16 weeks until end of study, participant dies, withdrawn consent, or lost to follow up (up to 18 months)
Part 1: Talquetamab Serum Concentrations	Serum concentrations will be calculated for Talquetamab.	Up to 4 weeks
Part 1: Number of Participants with Talquetamab Antibodies	Antibodies to Talquetamab will be assessed to evaluate potential immunogenicity.	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F. A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342.
• 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 MonumenTAL-1 study. Cancer. 2025 Jul 15;131(14):e35927. doi: 10.1002/cncr.35927.
• 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 of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study. Lancet Haematol. 2025 Apr;12(4):e269-e281. doi: 10.1016/S2352-3026(24)00385-5. Epub 2025 Mar 13.
• Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodriguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J, Verona R, Girgis S, Yang S, Goldsmith RB, Yao X, Pillarisetti K, Hilder BW, Russell J, Goldberg JD, Krishnan A. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022 Dec 15;387(24):2232-2244. doi: 10.1056/NEJMoa2204591. Epub 2022 Dec 10.
• 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 Nov 25;9(22):5752-5762. doi: 10.1182/bloodadvances.2025016613.
• 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.
• 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 Efficacy of Talquetamab vs. Real-World Physician's Choice of Treatment in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma: Updated Analyses of MonumenTAL-1 vs. LocoMMotion/MoMMent. Adv Ther. 2026 Jan;43(1):333-355. doi: 10.1007/s12325-025-03409-y. Epub 2025 Nov 28.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2017
• Primary Completion (Actual): July 7, 2022
• Study Completion (Estimated): October 20, 2027

Study Registration Dates

• First Submitted: December 22, 2017
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; talquetamab
• Other Study ID Numbers: CR108404; 2017-002400-26 (EudraCT Number); 64407564MMY1001 (Other Identifier: Janssen Research & Development, LLC); 2023-504581-29-00 (Registry Identifier: EUCT number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No