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

Phase 3Active Not RecruitingNCT05572515

Janssen Research & Development, LLC614 enrolled

Overview

The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd in Part 1 and to further characterize safety and efficacy of an alternative dosing for teclistamab in Part 2 in participants with relapsed or refractory multiple myeloma.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

614

Conditions

Relapsed or Refractory Multiple Myeloma

Interventions

TeclistamabDRUG

Teclistamab will be administered subcutaneously.

PomalidomideDRUG

Pomalidomide will be administered orally.

BortezomibDRUG

Bortezomib will be administered subcutaneously.

Dexamethasone

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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) * Received a maximum cumulative dose of corticosteroids of \>=140 mg of prednisone or equivalent within 14 days prior to randomization * Received a live, attenuated vaccine within 4 weeks before randomization * Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma * 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

Locations (211)

Outcomes

Primary Outcomes

Part 1: Progression-free Survival (PFS)

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.

Time frame: Up to 9 years

Part 2: Number of Participants Reporting Cytokine Release Syndrome (CRS) Cases by Severity

Severity for CRS will be graded as follows: Grade 1: Fever (Temperature greater than or equal to \[\>=\] 38°C); Grade 2: Fever (Temperature \>=38°C) with either: hypotension and/or hypoxia requiring low-flow nasal cannula or blow-by; Grade 3: Fever (Temperature \>=38°C) with either: hypotension and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask; Grade 4: Fever (Temperature \>=38°C) with either: hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure and Grade 5: Death.

Time frame: Up to 9 years

Secondary Outcomes

Part 1 and 2: Overall Response (Partial Response [PR] or Better)

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.

Time frame: Up to 9 years

Part 1 and 2: Very Good Partial Response (VGPR) or Better Response

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.

Time frame: Up to 9 years

Part 1 and 2: Complete Response (CR) or Better Response

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.

Data from ClinicalTrials.gov

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Dexamethasone will be administered orally in PVd and intravenously or orally in Kd.

CarfilzomibDRUG

Carfilzomib will be administered intravenously.

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

MemorialCare Long Beach Medical Center

Long Beach, California, United States

University of California Irvine

Orange, California, United States

PIH Health Hospital

Whittier, California, United States

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

University of Connecticut

Farmington, Connecticut, United States

University of Miami Sylvester Cancer Center

Miami, Florida, United States

Orlando Health Cancer Institute

Orlando, Florida, United States

...and 201 more locations

Time frame: Up to 9 years

Part 1: Duration of Response (DOR)

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 frame: Up to 9 years

Part 1: Time to Next Treatment (TTNT)

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

Time frame: Up to 9 years

Part 1: Progression-free Survival on Next-line Therapy (PFS2)

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 frame: Up to 9 years

Part 1: Overall Survival (OS)

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

Time frame: Up to 9 years

Part 1 and 2: Number of Participants with Adverse Events (AEs) by Severity

Number of participants with AEs by Severity will be reported.

Time frame: Up to 9 years

Part 1 and 2: Number of Participants with Serious Adverse Events (SAEs) by Severity

Number of participants with SAEs by Severity will be reported.

Time frame: Up to 9 years

Part 1 and 2: Number of Participants with Abnormal Laboratory Results

Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.

Time frame: Up to 9 years

Part 1 and 2: Serum Concentrations of Teclistamab

Serum concentrations of teclistamab will be reported.

Time frame: Up to 9 years

Part 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab

Number of participants with ADAs to teclistamab will be reported.

Time frame: Up to 9 years

Part 1: 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)

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.

Time frame: Baseline up to 9 years

Part 1: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score

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.

Time frame: Baseline up to 9 years

Part 1: 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)

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.

Time frame: Baseline up to 9 years

Part 1: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)

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 frame: Baseline up to 9 years

Part 1: Time to Worsening in Symptoms, Functioning, and Overall HRQoL

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.

Time frame: Up to 9 years

Part 1: PFS in Participants in High-risk Molecular Features

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.

Time frame: Up to 9 years

Part 1: Depth of Response in Participants in High-risk Molecular Features

Depth of response in participants in high-risk molecular features will be reported.

Time frame: Up to 9 years