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

Hematological Malignancies Clinical Trial

— MajesTEC-1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04557098
• Other study ID #: CR108859
• Secondary ID: 2016-002122-36TE
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 17, 2020
• Est. completion date: September 25, 2025

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

Study record NCT03145181 is Phase 1 part of this study and study record NCT04557098 is Phase 2 part of this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 194
• Est. completion date: September 25, 2025
• Est. primary completion date: March 13, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Multiple Myeloma

Intervention

Drug:
• Teclistamab
Teclistamab will be administered SC.

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent - UZ GENT	Gent
Belgium	Universitaire Ziekenhuizen Leuven	Leuven
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University Health Centre	Montreal	Quebec
Canada	University Health Network UHN Princess Margaret Cancer Centre	Toronto	Ontario
China	Peking University First Hospital	Beijing
China	West China Hospital Si Chuan University	Chengdu
China	Sun Yat -Sen University Cancer Center	Guangzhou
China	First affiliated Hospital of Zhejiang University	Hangzhou
China	Shanghai Changzheng Hospital	Shanghai
China	Shengjing Hospital Of China Medical University	Shenyang
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an
France	Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez	Lille Cedex
France	C.H.U. Hotel Dieu - France	Nantes
France	Centre Hospitalier Lyon Sud	Pierre Benite
France	CHRU Hôpital Jean Bernard	Poitiers
France	Pôle IUC Oncopole CHU	Toulouse cedex 9
France	CHRU Hôpital Bretonneau	Tours
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,	Tübingen
Germany	Universitatsklinikum Wurzburg	Wuerzburg
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi	Bologna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Netherlands	VU Medisch Centrum	Amsterdam
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon
Spain	Hosp Clinico Univ de Salamanca	Salamanca
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	Skane University Hospital	Lund
Sweden	Haematology Centre, R 51	Stockholm
United Kingdom	University College Hospital	London
United Kingdom	University Hospital Southampton	Sothampton
United Kingdom	Royal Marsden Hospital	Sutton
United States	Winship Cancer Institute Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  France,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2.9 years
Primary	Cohort D: 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.	Up to 2.9 years
Primary	Cohort D: 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.	Up to 2.9 years
Primary	Cohort D: 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.	Up to 2.9 years
Primary	Cohort D: 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.	Up to 2.9 years
Primary	Cohort D: Serum Concentration of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 3 months
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	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.	Up to 2.9 years
Secondary	Cohorts A and C: Serum Concentration of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 3 months
Secondary	Cohorts A and C: Number of Participants with Teclistamab Antibodies	Antibodies to teclistamab will be assessed to evaluate potential immunogenicity.	Up to 2.9 years
Secondary	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.	Baseline, up to 2.9 years
Secondary	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.	Baseline, up to 2.9 years
Secondary	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).	Baseline, up to 2.9 years
Secondary	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).	Up to 2.9 years

External Links

•   Dose Escalation Study of JNJ-64007957, a Humanized BCMA CD3 DuoBody® Antibody, in Participants With Relapsed or Refractory Multiple Myeloma