A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

Phase 2Active Not RecruitingNCT04557098

Janssen Research & Development, LLC194 enrolled

Overview

The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose (RP2D).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

194

Conditions

Hematological Malignancies

Interventions

TeclistamabDRUG

Teclistamab will be administered SC.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: - * Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 * Measurable disease: Cohort A and Cohort C: Multiple myeloma must be measurable by central laboratory assessment * A female participant of childbearing potential must have a negative pregnancy test at screening * Willing and able to adhere to the prohibitions and restrictions specified in this protocol * Cohort A: received at least \>=3 prior lines of therapy and previously received a PI, an IMiD and an anti-CD38 monoclonal antibody; Cohort C: received \>= 3 prior lines of therapy that included a PI, an IMiD, an anti-CD38 monoclonal antibody, and an anti-B cell maturation antigen (BCMA) treatment (with CART-T cells or an antibody drug conjugate (ADC) Exclusion Criteria: * Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light-chain amyloidosis * The following medical conditions: Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation, human immunodeficiency virus (HIV) infection, hepatitis B or C infection, stroke or seizure less than or equal to (\<=) 6 m, autoimmune disease, uncontrolled systemic infection, cardiac conditions (Myocardial Infarction \<= 6 m, stage III-IV congestive heart failure, etc) * Received any therapy that is targeted to BCMA, with the exception of Cohort C in Part 3 * Prior antitumor therapy, within 21 days (PI or radiotherapy within 14 days, IMiDs within 7 days, Gene modified adoptive cell therapy within 3 months) prior to first dose of study drug * Toxicities from previous anticancer therapies that have not resolved to baseline or to \<= grade 1 (except for alopecia or peripheral neuropathy) * Received a cumulative dose of corticosteroids equivalent to \>=140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication) * Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma (MM) * Myelodysplastic syndrome or active malignancies other than relapsed/refractory multiple myeloma with exceptions are: 1) Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured 2) Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. 3) Noninvasive cervical cancer treated within the last 24 months that is considered completely cured. 4) Localized prostate cancer (N0M0) 5) Breast cancer: Adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. 6) Malignancy that is considered cured with minimal risk of recurrence * Prior allogenic stem cell transplant \<=6 months * Prior autologous stem cell transplant \<=12 weeks * Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab

Locations (51)

Outcomes

Primary Outcomes

Cohorts A and C: Overall Response Rate (ORR)

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.

Time frame: Up to 2.9 years

Secondary Outcomes

Cohorts A and C: Duration of Response (DOR)

DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to PD, whichever occurs first.

Time frame: Up to 2.9 years

Cohorts A and C: Very Good Partial Response (VGPR) or Better Rate

VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.

Time frame: Up to 2.9 years

Cohorts A and C: Cohorts A and C: Complete Response (CR) or Better Rate

CR or better rate is defined as the percentage of patients who achieve a complete response (CR) or better according to IMWG response criteria.

Time frame: Up to 2.9 years

Cohorts A and C: Stringent Complete Response (sCR) Rate

sCR rate is defined as the percentage of patients who achieve a stringent complete response (sCR) according to IMWG response criteria.

Time frame: Up to 2.9 years

Cohorts A and C: Time to Response (TTR)

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.

Time frame: Up to 2.9 years

Data from ClinicalTrials.gov

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University of Alabama at Birmingham

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

University of California San Francisco

San Francisco, California, United States

Stanford University Medical Center

Stanford, California, United States

Winship Cancer Institute Emory University

Atlanta, Georgia, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

...and 41 more locations

Cohorts A and C: Progression-free Survival (PFS)

PFS is defined as the time from the date of first dose of study drug to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

Time frame: Up to 2.9 years

Cohorts A and C: Overall Survival (OS)

OS is defined as the time from the date of first dose of study drug to the date of the participant's death.

Time frame: Up to 2.9 years

Cohorts A and C: Minimal Residual Disease (MRD) Negative Rate

MRD-negative rate is defined as the proportion of participants who achieved MRD-negative status to a threshold of 10\^-5 at any timepoint after initial dose of teclistamab and before disease progression or starting subsequent therapy

Time frame: Up to 2.9 years

Cohorts A and C: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

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.

Time frame: Up to 2.9 years

Cohorts A and C: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability

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 experience, 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.

Time frame: Up to 2.9 years

Cohorts A and C: Number of Participants with AEs by Severity

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.

Time frame: Up to 2.9 years

Cohorts A and C: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values

Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.

Time frame: Up to 2.9 years

Cohorts A and C: Serum Concentration of Teclistamab

Serum concentrations of teclistamab will be reported.

Time frame: Up to 3 months

Cohorts A and C: Number of Participants with Teclistamab Antibodies

Antibodies to teclistamab will be assessed to evaluate potential immunogenicity.

Time frame: Up to 2.9 years

Cohorts A and C: 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)

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.

Time frame: Baseline, up to 2.9 years

Cohorts A and C: Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)

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.

Time frame: Baseline, up to 2.9 years

Cohorts A and C: Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)

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).

Time frame: Baseline, up to 2.9 years

Cohorts A and C: Overall Response Rate (ORR) in Participants with High-risk Molecular Features

ORR in participants with high risk is defined as the overall response rate among the high-risk molecular subgroups (del17p, t(4;14), t(14;16), or other high-risk molecular subtypes).

Time frame: Up to 2.9 years