A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

Phase 1

Active, not recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Teclistamab; Drug: Nirogacestat; Drug: Daratumumab; Drug: Lenalidomide; Drug: Pomalidomide; Drug: Bortezomib

• Registration Number: NCT04722146
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to characterize the safety and tolerability of teclistamab when administered in different combination regimen and to identify the optimal dose(s) of teclistamab combination regimens.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-20
• Study First Submitted QC: 2021-01-20
• Study First Posted: 2021-01-25
• Study Start: 2021-03-12
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-09
• Primary Completion: 2024-10-31
• Study Completion: 2025-02-24

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

• Have documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
• Meet treatment regimen-specific requirements as follows: Treatment Regimen A (teclistamab [tec]-daratumumab [dara]-pomalidomide [pom]) only: Participant has relapsed or refractory multiple myeloma and has received 1 to 3 prior lines of therapy, including exposure to a proteasome inhibitor (PI) and lenalidomide; Treatment Regimen B (tec-dara-lenalidomide [len]-bortezomib [bor]) only: Participant has newly diagnosed or relapsed/refractory multiple myeloma and is naive to treatment with lenalidomide; Treatment Regimen C (tec-nirogacestat [niro]) only: Participant has relapsed or refractory multiple myeloma and has 1) received 3 or more prior lines of therapy or 2) is double refractory to a PI and an immunomodulatory drug (IMiD) and triple exposed to a PI, an IMiD, and an anti-cluster of differentiation (CD)38 monoclonal antibody (mAb); Treatment Regimen D (tec-len) only: Participant has multiple myeloma and has received greater than or equal to (>=) 2 prior lines of therapy, including exposure to a PI, an IMiD, and an anti-CD38 mAb; Treatment Regimen E (tec-dara-len) only: Participant has newly diagnosed multiple myeloma or if previously treated has received 1 to 3 prior lines of therapy, including exposure to a PI and an IMiD; Treatment Regimen F (tec-dara-len-bor) only: Participant has newly diagnosed multiple myeloma
• Have measurable disease at screening as defined by at least one of the following: serum M-protein level >= 1.0 gram/deciliter (g/dL); or urine M-protein level >= 200 milligrams (mg)/24 hours; or light chain multiple myeloma: serum immunoglobulin (Ig) free light chain (FLC) >= 10 milligram/deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio
• A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin [hCG]) pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours before the start of study treatment administration and must agree to further serum or urine pregnancy tests during the study
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 100 days after the last dose of study treatment

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Exclusion Criteria

• Prior treatment with any therapy that targets B-cell maturation antigen (BCMA): This exclusion does not apply to Treatment Regimen C
• Live, attenuated vaccine within 30 days before the first dose of study treatment
• Received a cumulative dose of corticosteroids equivalent to >= 140 mg of prednisone within the 14-day period before the start of study treatment administration
• Active central nervous system (CNS) involvement or exhibition of clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required
• Known to be seropositive for human immunodeficiency virus

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles)	Bortezomib	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.
Treatment Regimen C: Teclistamab + Nirogacestat	Nirogacestat	Participants will receive teclistamab plus nirogacestat.
Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide	Lenalidomide	Participants will receive teclistamab plus daratumumab plus lenalidomide.
Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide	Teclistamab	Participants will receive teclistamab plus daratumumab plus pomalidomide.
Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide	Daratumumab	Participants will receive teclistamab plus daratumumab plus pomalidomide.
Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide	Pomalidomide	Participants will receive teclistamab plus daratumumab plus pomalidomide.
Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles)	Teclistamab	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.
Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles)	Daratumumab	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.
Treatment Regimen C: Teclistamab + Nirogacestat	Teclistamab	Participants will receive teclistamab plus nirogacestat.
Treatment Regimen D: Teclistamab + Lenalidomide	Teclistamab	Participants will receive teclistamab plus lenalidomide.
Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles)	Lenalidomide	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.
Treatment Regimen D: Teclistamab + Lenalidomide	Lenalidomide	Participants will receive teclistamab plus lenalidomide.
Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles)	Teclistamab	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.
Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide	Teclistamab	Participants will receive teclistamab plus daratumumab plus lenalidomide.
Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide	Daratumumab	Participants will receive teclistamab plus daratumumab plus lenalidomide.
Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles)	Daratumumab	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.
Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles)	Lenalidomide	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.
Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles)	Bortezomib	Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Abnormalities in Laboratory Values	Up to 2 year and 5 months	Number of participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.
Number of Participants with Dose-Limiting Toxicity (DLT)	Up to Cycle 2 Day 21 (each cycle is of 28 days for Treatment Regimen A and 21 days for Treatment Regimen B)	The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
Number of Participants with Incidence of Adverse Events (AEs)	Up to 2 year and 5 months	An AE can 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.
Number of Participants with AEs by Severity	Up to 2 year and 5 months	Number of participants with AEs by severity will be reported.

Secondary Outcome Measures

Name	Time	Method
Complete Response (CR) or Better Response Rate	Up to 2 year and 5 months	CR or better response rate is defined as the proportion of participants who achieve a CR or better response (sCR+CR) according to the IMWG 2016 criteria.
Stringent Complete Response (sCR) Rate	Up to 2 year and 5 months	sCR rate is defined as the proportion of participants who achieve an sCR according to the IMWG 2016 criteria.
Overall Response Rate (ORR)	Up to 2 year and 5 months	ORR is defined as the proportion of participants who achieve partial response (PR) or better according to the international myeloma working group (IMWG) 2016 criteria.
Duration of Response	Up to 2 year and 5 months	Duration of response is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria.
Time to Response	Up to 2 year and 5 months	Time to response is defined as the time between date of first dose of study treatment and the first efficacy evaluation at which the participant has met all criteria for PR or better.
Number of Participants with Presence of Anti-Drug Antibodies to Teclistamab	Up to 2 year and 5 months	Number of participants with anti-drug antibodies to teclistamab will be reported for all treatment regimens.
Number of Participants with Presence of Anti-Drug Antibodies to Daratumumab	Up to 2 year and 5 months	Number of participants with anti-drug antibodies to daratumumab will be reported for Treatment Regimen A, B, E and F.
Very Good Partial Response (VGPR) or Better Response Rate	Up to 2 year and 5 months	VGPR or better response rate is defined as the proportion of participants who achieve a VGPR or better response (stringent complete response \[sCR\]+ complete response \[CR\]+VGPR) according to the IMWG 2016 criteria.
Serum Concentrations of Teclistamab	Up to 2 year and 5 months	Serum concentrations of teclistamab will be reported.
Serum Concentrations of Nirogacestat	Up to 2 year and 5 months	Serum concentration of nirogacestat will be reported.
Number of Participants with Presence of Anti-Drug Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20)	Up to 2 year and 5 months	Number of participants with anti-drug antibodies to rHuPH20 will be reported for Treatment Regimen A, B, E and F.
Serum Concentrations of Daratumumab	Up to 2 year and 5 months	Serum concentrations of daratumumab will be reported.

Trial Locations

Locations (27)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Weill Cornell Medical College; 🇺🇸 New York, New York, United States

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

Washington University School Of Medicine; 🇺🇸 Saint Louis, Missouri, United States

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

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

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Indiana University Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

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

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

St Vincents Hospital Melbourne; 🇦🇺 Fitzroy, Australia

Medical College Of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Calvary Mater Newcastle Hospital; 🇦🇺 Waratah, Australia

UZ Gent; 🇧🇪 Gent, Belgium

CHU Nantes; 🇫🇷 Nantes Cedex 1, France

University College Hospital; 🇬🇧 London, United Kingdom

The Christie Nhs Foundation Trust; 🇬🇧 Manchester, United Kingdom

The Royal Marsden NHS Trust Sutton; 🇬🇧 Surrey, United Kingdom

Alfred Health; 🇦🇺 Melbourne, Australia

CHU de Bordeaux - Hospital Haut-Leveque; 🇫🇷 Pessac cedex, France

Chu Rennes Hopital Pontchaillou; 🇫🇷 Rennes, France

Institut Universitaire du cancer de Toulouse-Oncopole; 🇫🇷 TOULOUSE Cedex 9, France

UZA; 🇧🇪 Edegem, Belgium

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Centre Leon Berard; 🇫🇷 Lyon Cedex 8, France