Hematological Malignancies
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose (RP2D).
Interventions
DRUGTeclistamab
Teclistamab will be administered SC.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts A and C: Overall Response Rate (ORR) | Up to 2.9 years | 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
| Measure | Time frame | Description |
|---|---|---|
| Cohorts A and C: Duration of Response (DOR) | Up to 2.9 years | 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. |
| Cohorts A and C: Very Good Partial Response (VGPR) or Better Rate | Up to 2.9 years | VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria. |
| Cohorts A and C: Cohorts A and C: Complete Response (CR) or Better Rate | Up to 2.9 years | CR or better rate is defined as the percentage of patients who achieve a complete response (CR) or better according to IMWG response criteria. |
| Cohorts A and C: Stringent Complete Response (sCR) Rate | Up to 2.9 years | sCR rate is defined as the percentage of patients who achieve a stringent complete response (sCR) according to IMWG response criteria. |
| Cohorts A and C: Time to Response (TTR) | Up to 2.9 years | 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. |
| Cohorts A and C: Progression-free Survival (PFS) | Up to 2.9 years | 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. |
| Cohorts A and C: Overall Survival (OS) | Up to 2.9 years | OS is defined as the time from the date of first dose of study drug to the date of the participant's death. |
| Cohorts A and C: Minimal Residual Disease (MRD) Negative Rate | Up to 2.9 years | 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 |
| Cohorts A and C: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability | Up to 2.9 years | 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. |
| Cohorts A and C: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability | Up to 2.9 years | 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. |
| Cohorts A and C: Number of Participants with AEs by Severity | Up to 2.9 years | 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. |
| Cohorts A and C: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values | Up to 2.9 years | Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported. |
| Cohorts A and C: Serum Concentration of Teclistamab | Up to 3 months | Serum concentrations of teclistamab will be reported. |
| Cohorts A and C: Number of Participants with Teclistamab Antibodies | Up to 2.9 years | Antibodies to teclistamab will be assessed to evaluate potential immunogenicity. |
| 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) | Baseline, up to 2.9 years | 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. |
| Cohorts A and C: Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) | Baseline, up to 2.9 years | 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. |
| Cohorts A and C: Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) | Baseline, up to 2.9 years | 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). |
| Cohorts A and C: Overall Response Rate (ORR) in Participants with High-risk Molecular Features | Up to 2.9 years | 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). |
Countries
Belgium, Canada, China, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed