A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-9)

• ClinicalTrials.gov Identifier: NCT05572515
• Recruitment Status: Recruiting
• First Posted: October 7, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: October 5, 2022
• First Posted Date: October 7, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: March 29, 2023
• Estimated Primary Completion Date: October 14, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2022)

Progression-free Survival (PFS) [ Time Frame: Up to 9 years ]

PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International myeloma working group (IMWG) 2016 response criteria, or death due to any cause, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 2, 2023)

• Overall Response (Partial Response [PR] or Better) [ Time Frame: Up to 9 years ]
  Overall response (PR or better) is defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Very Good Partial Response (VGPR) or Better Response [ Time Frame: Up to 9 years ]
  VGPR or better (Stringent Complete Response [sCR]+Complete Response [CR]+VGPR) is defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Complete Response (CR) or Better Response [ Time Frame: Up to 9 years ]
  CR or better response is defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Duration of Response (DOR) [ Time Frame: Up to 9 years ]
  DOR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG 2016 response criteria or death due to any cause, whichever occurs first.
• Time to Next Treatment (TTNT) [ Time Frame: Up to 9 years ]
  TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment.
• Progression-free Survival on Next-line Therapy (PFS2) [ Time Frame: Up to 9 years ]
  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.
• Overall Survival (OS) [ Time Frame: Up to 9 years ]
  OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.
• Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: Up to 9 years ]
  Number of participants with AEs by Severity will be reported.
• Number of Participants with Serious Adverse Events (SAEs) by Severity [ Time Frame: Up to 9 years ]
  Number of participants with SAEs by Severity will be reported.
• Number of Participants with Abnormal Laboratory Results [ Time Frame: Up to 9 years ]
  Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.
• Serum Concentrations of Teclistamab [ Time Frame: Up to 9 years ]
  Serum concentrations of teclistamab will be reported.
• Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab [ Time Frame: Up to 9 years ]
  Number of participants with ADAs to teclistamab will be reported.
• Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by EORTC QLQ-C30 score version 3 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/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). 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/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days", and responses are reported on a 5-point verbal rating scale.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Baseline up to 6 months ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by PRO-CTCAE will be reported. The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting of treatment tolerability. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the AEs. It ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
• Time to Worsening in Symptoms, Functioning, and Overall HRQoL [ Time Frame: Up to 9 years ]
  Time to worsening in symptoms, functioning, and overall HRQoL will be measured as the interval from the date of randomization to the start date of meaningful change.
• PFS in Participants in High-risk Molecular Features [ Time Frame: Up to 9 years ]
  PFS in participants in high-risk molecular features will be reported. PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the IMWG 2016 response criteria, or death due to any cause, whichever occurs first.
• Depth of Response in Participants in High-risk Molecular Features [ Time Frame: Up to 9 years ]
  Depth of response in participants in high-risk molecular features will be reported.

Original Secondary Outcome Measures (submitted: October 5, 2022)

• Overall Response (Partial Response [PR] or Better) [ Time Frame: Up to 9 years ]
  Overall response (PR or better) is defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Very Good Partial Response (VGPR) or Better Response [ Time Frame: Up to 9 years ]
  VGPR or better (Stringent Complete Response [sCR]+Complete Response [CR]+VGPR) is defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Complete Response (CR) or Better Response [ Time Frame: Up to 9 years ]
  CR or better response is defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.
• Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to 9 years ]
  MRD negativity is defined as participants who achieve 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.
• Duration of Response (DOR) [ Time Frame: Up to 9 years ]
  DOR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG 2016 response criteria or death due to any cause, whichever occurs first.
• Time to Next Treatment (TTNT) [ Time Frame: Up to 9 years ]
  TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment.
• Progression-free Survival on Next-line Therapy (PFS2) [ Time Frame: Up to 9 years ]
  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.
• Overall Survival (OS) [ Time Frame: Up to 9 years ]
  OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.
• Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: Up to 9 years ]
  Number of participants with AEs by Severity will be reported.
• Number of Participants with Serious Adverse Events (SAEs) by Severity [ Time Frame: Up to 9 years ]
  Number of participants with SAEs by Severity will be reported.
• Number of Participants with Abnormal Laboratory Results [ Time Frame: Up to 9 years ]
  Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.
• Serum Concentrations of Teclistamab [ Time Frame: Up to 9 years ]
  Serum concentrations of teclistamab will be reported.
• Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab [ Time Frame: Up to 9 years ]
  Number of participants with ADAs to teclistamab will be reported.
• Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by EORTC QLQ-C30 score version 3 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/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). 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/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days", and responses are reported on a 5-point verbal rating scale.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Baseline up to 6 months ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by PRO-CTCAE will be reported. The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting of treatment tolerability. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the AEs. It ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) [ Time Frame: Baseline up to 9 years ]
  Change from baseline in symptoms, functioning, and overall HRQoL assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
• Time to Worsening in Symptoms, Functioning, and Overall HRQoL [ Time Frame: Up to 9 years ]
  Time to worsening in symptoms, functioning, and overall HRQoL will be measured as the interval from the date of randomization to the start date of meaningful change.
• PFS in Participants in High-risk Molecular Features [ Time Frame: Up to 9 years ]
  PFS in participants in high-risk molecular features will be reported. PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the IMWG 2016 response criteria, or death due to any cause, whichever occurs first.
• Depth of Response in Participants in High-risk Molecular Features [ Time Frame: Up to 9 years ]
  Depth of response in participants in high-risk molecular features will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma
• Official Title: A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal Antibody and Lenalidomide
• Brief Summary: The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd.
• Detailed Description: Multiple myeloma is an incurable, malignant, plasma cell disorder. Teclistamab (JNJ-64007957) is a full-size, Immunoglobulin G (IgG) 4 proline, alanine, and alanine (PAA) bispecific antibody that targets the cluster of differentiation (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). With its dual binding sites, teclistamab is able to draw CD3 positive T cells in close proximity to BCMA positive cells, resulting in T-cell activation and subsequent lysis of BCMA positive cells. Pomalidomide is a third-generation immunomodulatory imide drug (IMiD) that exerts potent, direct tumoricidal and immune-enhancing effects and Carfilzomib is a second-generation proteasome inhibitor that inhibits proteasome which results in disruption of protein turnover and induces apoptosis. The primary hypothesis of this study is that teclistamab monotherapy (Arm A) will significantly improve progression free survival (PFS) compared with investigator's choice of PVd or Kd (Arm B) in participants with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. The study will include a screening phase, treatment phase, and follow-up phase. Safety will be assessed by physical examinations, neurologic examinations, eastern cooperative oncology group (ECOG) performance status, clinical laboratory tests, vital signs, and AE monitoring. The overall duration of the study will be up to 9 years.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed or Refractory Multiple Myeloma

Intervention

• Drug: Teclistamab
  Teclistamab will be administered subcutaneously.
  Other Name: JNJ-64007957
• Drug: Pomalidomide
  Pomalidomide will be administered orally.
• Drug: Bortezomib
  Bortezomib will be administered subcutaneously.
• Drug: Dexamethasone
  Dexamethasone will be administered orally in PVd and intravenously or orally in Kd.
• Drug: Carfilzomib
  Carfilzomib will be administered intravenously.

Study Arms

• Experimental: Teclistamab
  Participants will receive teclistamab monotherapy.
  Intervention: Drug: Teclistamab
• Experimental: Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
  Participants will receive either PVd or Kd based on principal investigator's choice.
  Interventions:

  • Drug: Pomalidomide
  • Drug: Bortezomib
  • Drug: Dexamethasone
  • Drug: Carfilzomib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 5, 2022): 590
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2031
• Estimated Primary Completion Date: October 14, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Documented diagnosis of multiple myeloma as defined by the criteria below: (a)Multiple myeloma diagnosis according to International Myeloma Working Group (IMWG) diagnostic criteria (b) Measurable disease at screening as defined by any of the following: (1) Serum M-protein level greater than or equal to (>=)0.5 grams per deciliter (g/dL) (central laboratory); or (2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory); or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti- cluster of differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line
• Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator's determination of response by International myeloma working group (IMWG) criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
• Must be willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria:

• Received any prior B cell maturation antigen (BCMA)-directed therapy
• A participant is not eligible to receive PVd as control therapy if any of the following are present: (1) Received prior pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to randomization; A participant is not eligible to receive Kd as control therapy if any of the following are present:(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment (3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any adverse event [AE] related to carfilzomib)
• Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.
• Received a live, attenuated vaccine within 4 weeks before randomization
• Plasma cell leukemia at the time of screening, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid light chain amyloidosis
• Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, India, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Portugal, Spain, Sweden, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05572515
• Other Study ID Numbers: CR109244; 64007957MMY3006 ( Other Identifier: Janssen Research & Development, LLC ); 2022-000928-37 ( EudraCT Number ); 2023-503444-13-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024