A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma
- Registration Number
- NCT04634552
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 510
- Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
- Part 3: Measurable disease cohort A, cohort B, cohort C and cohort D: multiple myeloma must be measurable by central laboratory assessment; Cohort E: Multiple myeloma must be measurable by local laboratory assessment
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
- Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine
- Willing and able to adhere to the prohibitions and restrictions specified in this protocol
- Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B, Cohort D and Cohort E: T cell redirection therapy within 3 months
- Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
- Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
- Stroke or seizure within 6 months prior to signing the informed consent form (ICF)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 3: Cohort A (Talquetamab) Talquetamab Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (\>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the long-term extension (LTE) and will continue to receive study treatment. Part 3: Cohort B (Talquetamab) Talquetamab Cohort B will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment. Part 3: Cohort C (Talquetamab) Talquetamab Cohort C will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment. Part 3: Cohort D (Talquetamab) Talquetamab Cohort D will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants in this cohort will receive tocilizumab prophylaxis for cytokine release syndrome (CRS) including all outpatient dosing. Participants will transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment. Part 3: Cohort E (Talquetamab) Talquetamab Cohort E will enroll participants with multiple myeloma who have previously received at least 1 proteasome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-cluster of differentiation 38 (CD38) monoclonal antibody. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants will receive tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as possible transition to outpatient priming dosing transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Up to 2 years and 10 months ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Up to 2 years and 10 months DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria, or death due to PD, whichever occurs first.
Complete Response (CR) or Better Rate Up to 2 years and 10 months CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.
Progression-Free Survival (PFS) Up to 2 years and 10 months PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.
Stringent Complete Response (sCR) Rate Up to 2 years and 10 months sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.
Time to Response (TTR) Up to 2 years and 10 months TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.
Overall Survival (OS) Up to 2 years and 10 months OS is defined as the time from the date of first dose of study drug to the date of the participant's death.
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Up to 2 years and 10 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 Talquetamab Antibodies Up to 2 years and 10 months Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability Up to 2 years and 10 months An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Number of Participants with Abnormalities in Clinical Laboratory Values Up to 2 years and 10 months Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30) Baseline up to 2 years and 10 months The EORTC- QLQ-Core-30 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 recall period is 1 week ("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 higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Very Good Partial Response (VGPR) or Better Rate Up to 2 years and 10 months VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.
Minimal Residual Disease (MRD) Negative Rate Up to 2 years and 10 months MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.
Serum Concentration of Talquetamab Up to 2 years and 10 months Serum samples will be analyzed to determine concentrations of talquetamab.
Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) Baseline up to 2 years and 10 months The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).
Number of Participants with AEs by Severity Up to 2 years and 10 months Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Overall Response Rate (ORR) in Participants with High-risk Molecular Features Up to 2 years and 10 months ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.
Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) Baseline up to 2 years and 10 months 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). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.
Trial Locations
- Locations (77)
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
City of Hope
🇺🇸Duarte, California, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Emory University Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
NYU Langone Health
🇺🇸New York, New York, United States
Scroll for more (67 remaining)University of Alabama Birmingham🇺🇸Birmingham, Alabama, United States