A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)

• ClinicalTrials.gov Identifier: NCT04557098
• Recruitment Status: Active, not recruiting
• First Posted: September 21, 2020
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: September 17, 2020
• First Posted Date: September 21, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: September 17, 2020
• Estimated Primary Completion Date: March 13, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 9, 2022)

• Cohorts A and C: Overall Response Rate (ORR) [ Time Frame: 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.
• Cohort D: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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.
• Cohort D: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: 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.
• Cohort D: Number of Participants with AEs by Severity [ Time Frame: 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.
• Cohort D: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values [ Time Frame: Up to 2.9 years ]
  Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.
• Cohort D: Serum Concentration of Teclistamab [ Time Frame: Up to 3 months ]
  Serum concentrations of teclistamab will be reported.

Original Primary Outcome Measures (submitted: September 17, 2020)

Overall Response Rate (ORR) [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: November 9, 2022)

• Cohorts A and C: Duration of Response (DOR) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 3 months ]
  Serum concentrations of teclistamab will be reported.
• Cohorts A and C: Number of Participants with Teclistamab Antibodies [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: September 17, 2020)

• Duration of Response (DOR) [ Time Frame: 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.
• Very Good Partial Response (VGPR) or Better Rate [ Time Frame: 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.
• Complete Response (CR) or Better Rate [ Time Frame: 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.
• Stringent Complete Response (sCR) Rate [ Time Frame: 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.
• Time to Response (TTR) [ Time Frame: 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.
• Progression-free Survival (PFS) [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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.
• Minimal Residual Disease (MRD) Negative Rate [ Time Frame: Up to 2.9 years ]
  MRD-negative rate, as measured in participants who achieve CR/sCR, is defined as the proportion of participants who achieve MRD negative status.
• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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.
• Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [ Time Frame: 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.
• Number of Participants with AEs by Severity [ Time Frame: 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.
• Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values [ Time Frame: Up to 2.9 years ]
  Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.
• Serum Concentration of Teclistamab [ Time Frame: Up to 3 months ]
  Serum concentrations of teclistamab will be reported.
• Number of Participants with Teclistamab Antibodies [ Time Frame: Up to 2.9 years ]
  Antibodies to teclistamab will be assessed to evaluate potential immunogenicity.
• 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) [ Time Frame: 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.
• Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) [ Time Frame: 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.
• Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) [ Time Frame: 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).
• Overall Response Rate (ORR) in Participants with High-risk Molecular Features [ Time Frame: 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).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
• Official Title: A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
• Brief Summary: The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose (RP2D).
• Detailed Description: Study record NCT03145181 is Phase 1 part of this study and study record NCT04557098 is Phase 2 part of this study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hematological Malignancies

Intervention

Drug: Teclistamab

Teclistamab will be administered SC.

Other Name: JNJ-64007957

Study Arms

Experimental: Part 3: Teclistamab

Participants will receive teclistamab subcutaneously (SC) at recommended Phase 2 dose (RP2D) (Cohort A and Cohort C) and will receive alternative dosing schedule of teclistamab (Cohort D).

Intervention: Drug: Teclistamab

• Publications *: Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martinez-Lopez J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 10, 2023): 194
• Original Estimated Enrollment (submitted: September 17, 2020): 228
• Estimated Study Completion Date: September 25, 2025
• Estimated Primary Completion Date: March 13, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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, Cohort C and Cohort D: 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
• Cohorts A and D: received at least 3 prior MM treatment lines of therapy. Prior therapy must include an IMiD, PI, and 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, China, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04557098
• Other Study ID Numbers: CR108859; 2016-002122-36 ( EudraCT Number ); TECLIMMY1001-P3 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024