A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide

Phase 3

Recruiting

• Conditions: Relapsed or Refractory Multiple Myeloma
• Interventions: Drug: Talquetamab; Drug: Pomalidomide; Drug: Teclistamab; Drug: Elotuzumab; Drug: Dexamethasone; Drug: Bortezomib

• Registration Number: NCT06208150
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to compare the effectiveness of either talquetamab plus pomalidomide (Tal-P) or talquetamab plus teclistamab (Tal-Tec) with elotuzumab, pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib, and dexamethasone (PVd).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-05
• Study First Submitted QC: 2024-01-05
• Study First Posted: 2024-01-17
• Study Start: 2024-01-22
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-17
• Last Update Posted: 2025-07-18
• Primary Completion: 2026-04-23
• Study Completion: 2030-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 795

Inclusion Criteria

• Documented multiple myeloma as defined by the criteria below: (a) multiple myeloma diagnosis according to the international myeloma working group (IMWG) diagnostic criteria (b) measurable disease at screening as assessed by central laboratory, defined by any of the following: (i) serum M-protein level greater than or equal to (>=) 0.5 gram per deciliter (g/dL); or (ii) urine M-protein level >= 200 milligram (mg) per 24 hours; or (iii) light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
• Relapsed or refractory disease as defined below: a) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment
• Documented evidence of PD or failure to achieve a minimal response to the last line of therapy based on investigator's determination of response by 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
• A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6months after the last dose of study treatment

Exclusion Criteria

• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients
• Stroke, transient ischemic attack, or seizure within 6 months prior to signing informed consent form (ICF)
• Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment
• A maximum cumulative dose of corticosteroids of >=140 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Talquetamab + Pomalidomide (Tal-P)	Talquetamab	Participants will receive talquetamab as subcutaneous (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.
Arm A: Talquetamab + Pomalidomide (Tal-P)	Pomalidomide	Participants will receive talquetamab as subcutaneous (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.
Arm A: Talquetamab + Pomalidomide (Tal-P)	Dexamethasone	Participants will receive talquetamab as subcutaneous (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.
Arm B: Talquetamab + Teclistamab (Tal-Tec)	Talquetamab	Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
Arm B: Talquetamab + Teclistamab (Tal-Tec)	Dexamethasone	Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
Arm B: Talquetamab + Teclistamab (Tal-Tec)	Teclistamab	Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.
Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)	Pomalidomide	Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.
Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)	Elotuzumab	Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.
Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)	Dexamethasone	Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.
Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd)	Bortezomib	Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Up to 6 years 5 months	PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 6 years 5 months	ORR is defined as the percentage of participants with best overall response of partial response (PR) or better according to international myeloma working group (IMWG) response criteria.
Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)	Up to 6 years 5 months	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale.
Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)	Up to 6 years 5 months	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey	Up to 6 years 5 months	Change from baseline in symptoms, functioning, and HRQoL as assessed by epstein taste survey will be reported. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes. developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey.
Complete Response (CR) or Better Rate	Up to 6 years 5 months	CR or better is defined as the percentage of participants with best overall response of CR or better according to IMWG response criteria.
Minimal Residual Disease (MRD)-negative CR Rate	Up to 6 years 5 months	MRD-negative CR is defined as the percentage of participants who achieve both CR or better and MRD negativity at a threshold of 10\^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy (SST).
Overall Survival (OS)	Up to 6 years 5 months	OS is defined as the time from randomization to the date of participant's death.
Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30	Up to 6 years 5 months	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level.
Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Epstein Taste Survey	Up to 6 years 5 months	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The epstein taste survey consists of 17 items from the full 71 item PRO instrument, specific to taste changes developed for use in patients with head and neck cancer as a composite of the Vanderbilt Head and Neck Symptom Survey.
Very Good Partial Response (VGPR) or Better Rate	Up to 6 years 5 months	VGPR or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria.
Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab and Teclistamab	Up to 6 years 5 months	Number of participants with ADAs to talquetamab and teclistamab will be reported.
Time to Sustained Worsening in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by Patient Global Impression -Severity (PGI-S)	Up to 6 years 5 months	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from "none" to "very severe."
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by MySIm-Q	Up to 6 years 5 months	Change from baseline in symptoms, functioning, and HRQoL as assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific patient-reported outcome (PRO) assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC-QLQ-C30). It includes 17 items resulting in a symptom subscale and an impact subscale.
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30	Up to 6 years 5 months	Change from baseline in symptoms, functioning, and HRQoL as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems.
Percentage of Participants With Meaningful Improvement in HRQoL as Assessed by EORTC-QLQ-C30	Up to 6 years 5 months	Percentage of participants with meaningful improvement in HRQol as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea or vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high or healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale or item represents a high level of symptomatology or problems.
Progression Free Survival on Next-line Therapy (PFS2)	Up to 6 years 5 months	PFS2 is defined as time from randomization to progression on the next line of therapy or death, whichever comes first.
Time to Next Treatment (TTNT)	Up to 6 years 5 months	TTNT is defined as the time from randomization to the start of SST.
Serum Concentration of Talquetamab and Teclistamab	Up to 6 years 5 months	Serum concentration of talquetamab and teclistamab will be reported.
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by EQ-5D-5L	Up to 6 years 5 months	Change from baseline in symptoms, functioning, and HRQoL as assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by PGI-S	Up to 6 years 5 months	Change from baseline in symptoms, functioning, and HRQoL as assessed by PGI-S will be reported. The PGI-S will be used as an anchor, external criterion, to determine meaningful change in scores for the MySIm-Q and EORTC-QLQ-C30 in this population. The response options are presented as a 5-point verbal rating scale from "none" to "very severe."

Trial Locations

Locations (233)

UCSF Fresno; 🇺🇸 Clovis, California, United States

UCLA; 🇺🇸 Santa Monica, California, United States

Yale University School Of Medicine; 🇺🇸 New Haven, Connecticut, United States

Medical Oncology Hematology Consultants, PA; 🇺🇸 Newark, Delaware, United States

Memorial Healthcare System; 🇺🇸 Hollywood, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Winship Cancer Institute Emory University; 🇺🇸 Atlanta, Georgia, United States

Kootenai Health; 🇺🇸 Coeur d'Alene, Idaho, United States

University of Iowa Health Care; 🇺🇸 Waukee, Iowa, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Scroll for more (223 remaining)