A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma (MajesTEC-2)

A Multi-arm Phase 1b Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Teclistamab; Drug: Daratumumab; Drug: Pomalidomide; Drug: Lenalidomide; Drug: Bortezomib; Drug: Nirogacestat

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Fitzroy, Australia, 3065
    • St. Vincent's Hospital Melbourne
  • Melbourne, Australia, 3004
    • Alfred Health
  • Waratah, Australia, 2298
    • Calvary Mater Newcastle Hospital
• Belgium
  • Edegem, Belgium, 2650
    • UZA
  • Gent, Belgium, 9000
    • UZ Gent
• France
  • Lyon Cedex 8, France, 69373
    • Centre Leon Berard
  • Nantes Cedex 1, France, 44093
    • CHU Nantes
  • Pessac cedex, France, 33604
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Rennes, France, 35000
    • Chu Rennes Hopital Pontchaillou
  • TOULOUSE Cedex 9, France, 31059
    • Institut Universitaire du cancer de Toulouse-Oncopole
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • University College Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Surrey, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Trust Sutton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1032
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide; Participants will receive teclistamab plus daratumumab plus pomalidomide.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Daratumumab; Participants will receive daratumumab.; Drug: Pomalidomide; Participants will receive pomalidomide.
Experimental: Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles); Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Daratumumab; Participants will receive daratumumab.; Drug: Lenalidomide; Participants will receive lenalidomide.; Drug: Bortezomib; Participants will receive bortezomib.
Experimental: Treatment Regimen C: Teclistamab + Nirogacestat; Participants will receive teclistamab plus nirogacestat.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Nirogacestat; Participants will receive nirogacestat.
Experimental: Treatment Regimen D: Teclistamab + Lenalidomide; Participants will receive teclistamab plus lenalidomide.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Lenalidomide; Participants will receive lenalidomide.
Experimental: Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide; Participants will receive teclistamab plus daratumumab plus lenalidomide.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Daratumumab; Participants will receive daratumumab.; Drug: Lenalidomide; Participants will receive lenalidomide.
Experimental: Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles); Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.	Drug: Teclistamab; Participants will receive teclistamab.; Other Names: JNJ-64007957; Drug: Daratumumab; Participants will receive daratumumab.; Drug: Lenalidomide; Participants will receive lenalidomide.; Drug: Bortezomib; Participants will receive bortezomib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Incidence of Adverse Events (AEs)	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.	Up to 2 year and 5 months
Number of Participants with AEs by Severity	Number of participants with AEs by severity will be reported.	Up to 2 year and 5 months
Number of Participants with Abnormalities in Laboratory Values	Number of participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.	Up to 2 year and 5 months
Number of Participants with Dose-Limiting Toxicity (DLT)	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.	Up to Cycle 2 Day 21 (each cycle is of 28 days for Treatment Regimen A and 21 days for Treatment Regimen B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	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.	Up to 2 year and 5 months
Very Good Partial Response (VGPR) or Better Response Rate	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.	Up to 2 year and 5 months
Complete Response (CR) or Better Response Rate	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.	Up to 2 year and 5 months
Stringent Complete Response (sCR) Rate	sCR rate is defined as the proportion of participants who achieve an sCR according to the IMWG 2016 criteria.	Up to 2 year and 5 months
Duration of Response	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.	Up to 2 year and 5 months
Time to Response	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.	Up to 2 year and 5 months
Serum Concentrations of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 2 year and 5 months
Serum Concentrations of Daratumumab	Serum concentrations of daratumumab will be reported.	Up to 2 year and 5 months
Serum Concentrations of Nirogacestat	Serum concentration of nirogacestat will be reported.	Up to 2 year and 5 months
Number of Participants with Presence of Anti-Drug Antibodies to Teclistamab	Number of participants with anti-drug antibodies to teclistamab will be reported for all treatment regimens.	Up to 2 year and 5 months
Number of Participants with Presence of Anti-Drug Antibodies to Daratumumab	Number of participants with anti-drug antibodies to daratumumab will be reported for Treatment Regimen A, B, E and F.	Up to 2 year and 5 months
Number of Participants with Presence of Anti-Drug Antibodies to Recombinant Human Hyaluronidase PH20 Enzyme (rHuPH20)	Number of participants with anti-drug antibodies to rHuPH20 will be reported for Treatment Regimen A, B, E and F.	Up to 2 year and 5 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research and Development, LLC Clinical Trial, Janssen Research and Development LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2021
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): February 24, 2025

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gamma Secretase Inhibitors and Modulators; Pomalidomide; Lenalidomide; Daratumumab; Bortezomib; Nirogacestat
• Other Study ID Numbers: CR108927; 2020-004404-33 (EudraCT Number); 64007957MMY1004 (Other Identifier: Janssen Research & Development, LLC); 2023-503440-14-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No