Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05455320

A Study Comparing Talquetamab in Combination With Daratumumab or in Combination With Daratumumab and Pomalidomide Versus Daratumumab in Combination With Pomalidomide and Dexamethasone in Participants With Multiple Myeloma That Returns After Treatment or is Resistant to Treatment

The purpose of the study is to compare the efficacy of talquetamab subcutaneous(ly) (SC) in combination with daratumumab SC and pomalidomide (Tal-DP) and talquetamab SC in combination with daratumumab SC (Tal-D), respectively, with daratumumab SC in combination with pomalidomide and dexamethasone (DPd).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

UZ Brussel, Brussels, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Documented multiple myeloma as defined: a) Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria and b) Measurable disease at screening as defined by any of the following: i) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL) (central laboratory); ii) Urine M-protein level >= 200 milligram (mg) per 24 hours (central laboratory); iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain >= 10 milligram per deciliter (mg/dL) (central laboratory), and abnormal serum immunoglobulin kappa lambda free light chain ratio
  • Relapsed or refractory disease as defined by: i) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease by IMWG criteria greater than (>) 60 days after cessation of treatment; ii) Refractory disease is defined as less than (<) 25 percent (%) reduction in monoclonal paraprotein (M-protein) or confirmed progressive disease by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment
  • Received at least 1 prior line of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide. Participants who have received only 1 prior line of antimyeloma therapy must be considered lenalidomide-refractory (that is, have demonstrated progressive disease by IMWG criteria on or within 60 days of completion of lenalidomide-containing regimen). Participants who have received >=2 prior lines of antimyeloma therapy must be considered lenalidomide exposed
  • Documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or after their last regimen
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment

Exclusion criteria

  • Contraindications or life-threatening allergies, hypersensitivity, or intolerance to study drug excipients
  • Disease is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody as defined per IMWG consensus guidelines (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody)
  • Received prior pomalidomide therapy
  • A maximum cumulative dose of corticosteroids to >=140 milligrams (mg) of prednisone or equivalent within 14-day period before the first dose of study drug
  • Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
  • Plasma cell leukemia (per IMWG criteria) at the time of screening, Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS syndrome), or primary amyloid light chain amyloidosis

Treatment and study plan

Talquetamab

Drug

Talquetamab will be administered subcutaneously.

Other names: JNJ-64407564

Daratumumab

Drug

Daratumumab will be administered subcutaneously.

Pomalidomide

Drug

Pomalidomide will be administered orally.

Dexamethasone

Drug

Dexamethasone will be administered orally or intravenously.

Primary outcomes

  1. Progression-Free Survival (PFS)

    Time frame: Up to 6 years 6 months

    PFS is defined as time from the date of randomization to the first documentation of disease progression, or death due to any cause, whichever is reported first.

Secondary outcomes

  1. Overall Response (Partial Response [PR] or Better)

    Time frame: Up to 6 years 6 months

    Overall response (PR or better) is defined as percentage of participants who have a PR or better per International Myeloma Working Group (IMWG) criteria.

  2. Very Good Partial Response (VGPR) or Better Rate

    Time frame: Up to 6 years 6 months

    VGPR or better rate is defined as the percentage of participants who achieve a VGPR or better according to IMWG response criteria.

  3. Complete Response (CR) or Better Rate

    Time frame: Up to 6 years 6 months

    CR or better rate is defined as the percentage of participants who achieve CR or better according to IMWG response criteria.

  4. Overall Minimal Residual Disease (MRD) Negative CR

    Time frame: Up to 6 years 6 months

    MRD-negative CR is defined as proportion of participants with CR or stringent CR who achieve MRD negativity at a threshold of 10^-5 at any timepoint after the first dose of study drug and before disease progression or start of subsequent antimyeloma therapy.

  5. Overall Survival (OS)

    Time frame: Up to 6 years 6 months

    OS is defined as the time from the date of randomization to the date of the participant's death.

  6. Progression-free Survival on Next-line Therapy (PFS2)

    Time frame: Up to 6 years 6 months

    PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.

  7. Time to Next Therapy (TTNT)

    Time frame: Up to 6 years 6 months

    TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment.

  8. Number of Participants with Adverse Events (AEs)

    Time frame: Up to 6 years 6 months

    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.

  9. Number of Participants with AEs by Severity

    Time frame: Up to 6 years 6 months

    Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

  10. Serum Concentrations of Talquetamab

    Time frame: Up to 6 years 6 months

    Serum concentrations of talquetamab will be reported.

  11. Serum Concentrations of Daratumumab

    Time frame: Up to 6 years 6 months

    Serum concentrations of daratumumab will be reported.

  12. Number of Participants with Presence of Anti-Drug Antibodies (ADAs) to Talquetamab

    Time frame: Up to 6 years 6 months

    Number of participants with presence ADAs to talquetamab will be reported.

  13. Number of Participants With Presence of Anti-Drug Antibodies (ADAs) to Daratumumab

    Time frame: Up to 6 years 6 months

    Number of participants with presence of ADAs to daratumumab will be reported.

  14. Time to Worsening in Symptoms, Functioning, and Overall Health-Related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)

    Time frame: Up to 6 years 6 months

    The MySIm-Q is a disease-specific PRO assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30).

  15. Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PROMIS Short Form Version 2.0 -Physical Functioning 8c

    Time frame: Up to 6 years 6 months

    The Patient-reported Outcomes Measurement Information System (PROMIS) Short Form Version 2.0 -Physical Function 8c is an 8-item fixed--length short form derived from the PROMIS Physical Function item bank.

  16. Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by EORTC-QLQ-C30

    Time frame: Up to 6 years 6 months

    Time to worsening in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 will be reported.

  17. Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PRO-CTCAE

    Time frame: Up to 6 years 6 months

    The National Cancer Institute's (NCI) PRO-CTCAE is an item library of common AEs experienced by people with cancer that are appropriate for self-reporting of treatment tolerability.

  18. Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)

    Time frame: Up to 6 years 6 months

    The EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses.

  19. Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)

    Time frame: Up to 6 years 6 months

    The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and PROMIS SF PF 8c in this population.

  20. Change From Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)

    Time frame: Baseline up to 6 years 6 months

    The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30.

  21. Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by PROMIS Short Form Version 2.0 -Physical Functioning 8c

    Time frame: Baseline up to 6 years 6 months

    The Patient-reported Outcomes Measurement Information System (PROMIS) Short Form Version 2.0 -Physical Function 8c is an 8-item fixed-length short form derived from the PROMIS Physical Function item bank.

  22. Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by EORTC-QLQ-C30

    Time frame: Baseline up to 6 years 6 months

    Change from baseline in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 will be reported.

  23. Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by PRO-CTCAE

    Time frame: Baseline up to 6 years 6 months

    The National Cancer Institute's (NCI) PRO-CTCAE is an item library of common AEs experienced by people with cancer that are appropriate for self-reporting of treatment tolerability.

  24. Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)

    Time frame: Baseline up to 6 years 6 months

    The EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses.

  25. Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)

    Time frame: Baseline up to 6 years 6 months

    The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and PROMIS SF PF 8c in this population.

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

A Phase 3 Randomized Study Comparing Talquetamab SC in Combination With Daratumumab SC and Pomalidomide (Tal-DP) or Talquetamab SC in Combination With Daratumumab SC (Tal-D) Versus Daratumumab SC, Pomalidomide and Dexamethasone (DPd), in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received at Least 1 Prior Line of Therapy

Acronym: MonumenTAL-3

Important dates

Study start
2022
Primary completion
2027
Study completion
2028
First posted
Jul 13, 2022
Registry last updated
Jun 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.