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

JRCT ID: jRCT2051220102

Registered date:07/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed or Refractory Multiple Myeloma
• Date of first enrollment: 06/12/2022
• Target sample size: 810
• Countries of recruitment: Belgium,Japan,Brazil,Japan,China,Japan,Czechia,Japan,Germany,Japan,Spain,Japan,France,Japan,UnitedKingdom Of Great Britain And NorthernIreland,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Korea,Republic Of,Japan,Netherlands,Japan,Poland,Japan,Turkey,Japan,Taiwan,Japan,UnitedStates Of America,Japan
• Study type: Interventional

Intervention(s)

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.

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.

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.

Outcome(s)

• Primary Outcome: Progression-Free Survival (PFS) : 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 Outcome

Overall Response (Partial Response [PR] or Better) : 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 : 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 : 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 Status : 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) : 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) : 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) : 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) : 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 : 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 : Up to 6 years 6 months : Serum concentrations of talquetamab will be reported.

Serum Concentrations of Daratumumab : 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 : 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 : 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) : 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 : 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 : 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 : 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) : 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) : 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) : 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 : 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 : 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 : 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) : 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) : 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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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,
Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly,
endocrinopathy, M-protein, and skin changes (POEMS syndrome), or primary
amyloid light chain amyloidosis

Related Information

• Primary Sponsor: Nishikawa Kazuko
• Secondary ID(s): NCT05455320