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

Phase 2

Active, not recruiting

• Conditions: Hematological Malignancies
• Interventions: Drug: Teclistamab

• Registration Number: NCT04557098
• Lead Sponsor: Janssen Research & Development, LLC

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 Timeline

• Study Start: 2020-09-17
• Study First Submitted: 2020-09-17
• Study First Submitted QC: 2020-09-17
• Study First Posted: 2020-09-21
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Primary Completion: 2025-03-13
• Study Completion: 2026-06-26

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 194

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)

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part 3: Teclistamab	Teclistamab	Participants will receive teclistamab subcutaneously (SC) at recommended Phase 2 dose (RP2D) in Cohort A and Cohort C.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (54)

Winship Cancer Institute Emory University; 🇺🇸 Atlanta, Georgia, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University Health Network UHN Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Peking University First Hospital; 🇨🇳 Beijing, China

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Sahlgrenska University Hospital; 🇸🇪 Göteborg, Sweden

West China Hospital Si Chuan University; 🇨🇳 Chengdu, China

Sun Yat -Sen University Cancer Center; 🇨🇳 Guangzhou, China

Levine Cancer Institute; 🇺🇸 Charlotte, North Carolina, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Universitair Ziekenhuis Gent - UZ GENT; 🇧🇪 Gent, Belgium

First affiliated Hospital of Zhejiang University; 🇨🇳 Hangzhou, China

Clinica Univ. de Navarra; 🇪🇸 Pamplona, Spain

Shanghai Changzheng Hospital; 🇨🇳 Shanghai, China

Shengjing Hospital Of China Medical University; 🇨🇳 Shenyang, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, China

Azienda Ospedaliera Papa Giovanni XXIII; 🇮🇹 Bergamo, Italy

Universitaetsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Universitaetsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Universitatsklinikum Wurzburg; 🇩🇪 Wuerzburg, Germany

Hosp. Quiron Madrid Pozuelo; 🇪🇸 Pozuelo de Alarcon, Spain

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Hosp Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,; 🇩🇪 Tübingen, Germany

The Second Affiliated Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, China

VU Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi; 🇮🇹 Bologna, Italy

Hosp. Univ. 12 de Octubre; 🇪🇸 Madrid, Spain

Hosp. Univ. Germans Trias I Pujol; 🇪🇸 Badalona, Spain

Haematology Centre, R 51; 🇸🇪 Stockholm, Sweden

University College Hospital; 🇬🇧 London, United Kingdom

Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

University Hospital Southampton; 🇬🇧 Sothampton, United Kingdom

C.H.U. Hotel Dieu - France; 🇫🇷 Nantes, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez; 🇫🇷 Lille Cedex, France

CHRU Hôpital Jean Bernard; 🇫🇷 Poitiers, France

Pôle IUC Oncopole CHU; 🇫🇷 Toulouse cedex 9, France

CHRU Hôpital Bretonneau; 🇫🇷 Tours, France

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

Hosp Clinico Univ de Salamanca; 🇪🇸 Salamanca, Spain

Hosp. Univ. Marques de Valdecilla; 🇪🇸 Santander, Spain

City of Hope; 🇺🇸 Duarte, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Skane University Hospital; 🇸🇪 Lund, Sweden

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Universitaire Ziekenhuizen Leuven; 🇧🇪 Leuven, Belgium

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects; 🇺🇸 New York, New York, United States

Arthur J. E. Child Comprehensive Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Arthur J E Child Comprehensive Cancer Centre; 🇨🇦 Calgary, Alberta, Canada