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 (MonumenTAL-3)
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ClinicalTrials.gov Identifier: NCT05455320 |
Recruitment Status :
Recruiting
First Posted : July 13, 2022
Last Update Posted : November 8, 2023
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Condition or disease | Intervention/treatment | Phase |
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Relapsed or Refractory Multiple Myeloma | Drug: Talquetamab Drug: Daratumumab Drug: Pomalidomide Drug: Dexamethasone | Phase 3 |
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 810 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | October 13, 2022 |
Estimated Primary Completion Date : | February 6, 2026 |
Estimated Study Completion Date : | April 6, 2029 |

Arm | Intervention/treatment |
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Experimental: Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP)
Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
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Drug: Talquetamab
Talquetamab will be administered subcutaneously.
Other Name: JNJ-64407564 Drug: Daratumumab Daratumumab will be administered subcutaneously. Drug: Pomalidomide Pomalidomide will be administered orally. Drug: Dexamethasone Dexamethasone will be administered orally or intravenously. |
Experimental: Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd)
Participants will receive daratumumab as SC injection; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
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Drug: Daratumumab
Daratumumab will be administered subcutaneously. Drug: Pomalidomide Pomalidomide will be administered orally. Drug: Dexamethasone Dexamethasone will be administered orally or intravenously. |
Experimental: Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D)
Participants will receive talquetamab and daratumumab as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
|
Drug: Talquetamab
Talquetamab will be administered subcutaneously.
Other Name: JNJ-64407564 Drug: Daratumumab Daratumumab will be administered subcutaneously. Drug: Dexamethasone Dexamethasone will be administered orally or intravenously. |
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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).
- Serum Concentrations of Talquetamab [ Time Frame: Up to 6 years 6 months ]Serum concentrations of talquetamab will be reported.
- Serum Concentrations of Daratumumab [ Time Frame: Up to 6 years 6 months ]Serum concentrations of daratumumab will be reported.
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
- 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)
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05455320
Contact: Study Contact | 844-434-4210 | Participate-In-This-Study@its.jnj.com | |
Contact: Mel McMahon | 888-850-0650 | mel@sparkcures.com |

Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Responsible Party: | Janssen Research & Development, LLC |
ClinicalTrials.gov Identifier: | NCT05455320 |
Other Study ID Numbers: |
CR109082 2021-000202-22 ( EudraCT Number ) 64407564MMY3002 ( Other Identifier: Janssen Research & Development, LLC ) 2023-503467-41-00 ( Registry Identifier: EUCTR number ) |
First Posted: | July 13, 2022 Key Record Dates |
Last Update Posted: | November 8, 2023 |
Last Verified: | November 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu |
URL: | https://www.janssen.com/clinical-trials/transparency |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Daratumumab Pomalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors |