A Study of Teclistamab in Japanese Participants With Relapsed or Refractory Multiple Myeloma
- Registration Number
- NCT04696809
- Lead Sponsor
- Janssen Pharmaceutical K.K.
- Brief Summary
The purpose of the study is to evaluate the safety and tolerability in Japanese participants with relapsed or refractory multiple myeloma (RRMM) at the recommended Phase 2 dose (RP2D) identified in Study 64007957MMY1001 (NCT03145181) in Phase 1 part and to evaluate the efficacy of teclistamab at RP2D for Japanese participants in Phase 2 part.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Japanese Participants with Relapsed or Refractory Multiple Myeloma (MM) Teclistamab Japanese participants will receive Teclistamab subcutaneously (SC) at four dose levels. Cohort 1 will receive Teclistamab at Dose 1 and 2 (step-up doses) prior to first treatment dose on Day 1 followed by Dose 3 weekly (that is, on Days 1,8, and 15 of a 21-day cycle). Cohort 2 will receive Teclistamab at Dose 1 and 4 (step up doses) prior to first treatment dose on Day 1 followed by Dose 5 weekly. Cohort 3 will receive Teclistamab at Dose 1, 4, and 5 (step up doses) prior to first treatment dose on Day 1 followed by Dose 6 weekly. Cohort 4 will receive Teclistamab at Dose 1, 4, and 5 (step up doses) prior to first treatment dose on Day 1 followed by Dose 7 weekly for (2 cycles), then biweekly (cycle 3 to 6) on Days 1 and 15 and monthly (cycle 7) on Day 1 of 1 28-day cycle. In Phase 2 , participants will receive Teclistamab SC at Dose 1 and 4 (step up doses) up to 8 days prior to first treatment dose on Day 1 followed by Dose 5 on Days 1,8,15, and 22 of a 28-day cycle.
- Primary Outcome Measures
Name Time Method Phase 1: Number of Participants with Serious Adverse Events (SAE) Up to 1 year and 5 months A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Phase 1: Number of Participants with Dose Limiting Toxicity (DLT) Up to 28 days Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Phase 1: Number of Participants with Adverse Events (AE) Up to 1 year and 5 months An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
Phase 2: Overall response rate (ORR) Up to 1 year and 5 months ORR is defined as the percentage of participants who have a partial response (PR) or better according to the 2016 International Myeloma Working Group (IMWG) response criteria.
- Secondary Outcome Measures
Name Time Method Phase 2: Number of Participants with SAEs by Severity Up to 1 year and 5 months Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.
Phase 2: Change from Baseline in Health-related Quality of Life (HRQoL) (Symptoms, Functioning, and Well-being) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Up to 1 year and 5 months Change from baseline in EORTC- QLQ-C30 score 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 higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Phase 1: Objective Response Rate Up to 1 year and 5 months Objective response will be defined as partial response (PR) or better as defined by the 2016 IMWG response criteria in multiple myeloma (MM).
Phase 1 and Phase 2: Serum Concentration of Teclistamab Up to 1 year and 5 months Serum concentration of Teclistamab will be assessed.
Phase 1: Systemic Cytokine Concentrations Up to 1 year and 5 months Cytokines concentration will be measured for biomarker assessment.
Phase 1 and Phase 2: Number of Participants with Anti-teclistamab Antibodies Up to 1 year and 5 months Number of participants with anti-teclistamab antibodies will be assessed.
Phase 2: Change from Baseline in EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) Scale Up to 1 year and 5 months Change from baseline in EQ-5D-5L scale will be reported. The EQ-5D-5L is a generic measure of health status. 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).
Phase 2: Overall survival (OS) Up to 1 year and 5 months OS is defined as the time from the date of first dose of study drug to the date of the participant's death. If the participant is alive or the vital status is unknown, then the participant's data will be censored at the date the participant was last known to be alive.
Phase 2: Minimal Residual Disease (MRD)-negative Rate Up to 1 year and 5 months MRD-negative rate is defined as the percentage 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.
Phase 2: Number of Participants with AEs Up to 1 year and 5 months An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.
Phase 2: Number of Participants with AEs by Severity Up to 1 year and 5 months Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.
Phase 2: Number of Participants with SAEs Up to 1 year and 5 months A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.
Phase 2: Number of Participants with Abnormalities in Clinical Laboratory Test Values Up to 1 year and 5 months Number of participants with abnormalities in clinical laboratory test values of hematology, serum chemistry, and coagulation will be reported.
Phase 1 and Phase 2: Duration of Response (DOR) Up to 1 year and 5 months DOR is defined as the duration 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 2016 IMWG criteria, or death.
Phase 1 and Phase 2: Time to Response (TTR) Up to 1 year and 5 months TTR is defined as the time between date of first dose of study treatment and the first efficacy evaluation that the participant has met all criteria for PR or better.
Phase 2: Very Good Partial Response (VGPR) or Better Response Rate (Stringent Complete Response [sCR]+ Complete Response [CR]+VGPR) Up to 1 year and 5 months VGPR or better response rate (sCR+CR+VGPR) is defined as the percentage of participants who achieve a VGPR or better response according to the 2016 IMWG response criteria.
Phase 2: Complete Response (CR) or Better Response Rate Up to 1 year and 5 months CR or better response rate is defined as the percentage of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.
Phase 2: Stringent Complete Response (sCR) Rate Up to 1 year and 5 months sCR rate is defined as the percentage of participants who achieve an sCR according to the IMWG 2016 criteria.
Phase 2: Progression-free Survival (PFS) Up to 1 year and 5 months 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 2016 IMWG response criteria, or death due to any cause, whichever occurs first.
Phase 2: Number of Participants with Abnormalities in Clinical Laboratory Test Values by Severity Up to 1 year and 5 months Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 with the exception of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. 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.
Phase 2: Change from Baseline in Patient Global Impression of Severity (PGIS) Scale Up to 1 year and 5 months Change from baseline in PGIS scale will be reported. The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale (1: None, 2: Mild, 3: Moderate, 4: Severe, 5: Very Severe) at the time of completing the PRO measure. Higher score indicate greater severity.
Trial Locations
- Locations (15)
National Hospital Organization Okayama Medical Center
🇯🇵Okayama, Japan
Kameda Medical Center
🇯🇵Chiba, Japan
Ogaki Municipal Hospital
🇯🇵Gifu, Japan
Kobe City Medical Center General Hospital
🇯🇵Kobe City, Japan
Kurume University Hospital
🇯🇵Kurume, Japan
Japanese Red Cross Osaka Hospital
🇯🇵Osaka, Japan
National Hospital Organization Hiroshima-Nishi Medical Center
🇯🇵Otake, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya, Japan
National Hospital Organization Mito Medical Center
🇯🇵Higashiibaraki-gun, Japan
National Hospital Organization Kumamoto Medical Center
🇯🇵Kumamoto shi, Japan
Kyoto Kuramaguchi Medical Center
🇯🇵Kyoto, Japan
Nagoya City University Hospital
🇯🇵Nagoya City, Japan
National Hospital Organization Matsumoto Medical Center
🇯🇵Matsumoto, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Osaka International Cancer Institute
🇯🇵Osaka City, Japan