Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT03399799 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: CR10840464407564MMY10012017-002400-262023-504581-29-00
• Study Type: interventional
• Target: 279
• Locations: 4 countries
• Sites: 13

Brief Summary

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 \[Dose Expansion\]).

Conditions

Hematological Malignancies

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Part 1: Talquetamab Serum Concentrations

  Up to 4 weeks

• Part 1 and Part 2: Biomarker Assessment

  Up to Cycle 7 Day 1 (each cycle of 21-days)

• Part 1: Number of Participants with Talquetamab Antibodies

  Up to 4 weeks

• Part 2: Overall Response Rate (ORR)

  Approximately 2.10 years

• Part 2: Clinical Benefit Rate (CBR)

  Approximately 2.10 years

Study Arms (3)

Part 1: Dose Escalation (Talquetamab) - Intravenous (IV)

EXPERIMENTAL

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

Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC)

EXPERIMENTAL

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

Part 2: Dose Expansion (Talquetamab)

EXPERIMENTAL

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

Interventions

Talquetamab DRUG

Participants will receive IV infusion or SC injection of Talquetamab.

Part 1: Dose Escalation (Talquetamab) - Intravenous (IV); Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC); Part 2: Dose Expansion (Talquetamab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (13)

University of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, 4000, Belgium

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

UMCU

Utrecht, 3584 CX, Netherlands

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, 28223, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Related Publications (7)

• 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.

  PMID: 41313549 DERIVED

• 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.

  PMID: 40864183 DERIVED

• 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.

  PMID: 40631904 DERIVED

• 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.

  PMID: 40090350 DERIVED

• 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 DERIVED

• 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.

  PMID: 36507686 DERIVED

• 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.

  PMID: 32040549 DERIVED

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

talquetamab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 16, 2018
• Study Start: December 16, 2017
• Primary Completion: July 7, 2022
• Study Completion (Estimated): October 20, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

BE (1); US (5); NL (2); ES (5)