Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)

A Phase 1, 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

The purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for Teclistamab and to characterize the safety and tolerability of Teclistamab at the RP2Ds.

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Teclistamab (IV); Drug: Teclistamab(SC)

Detailed Description

The study will be conducted in 2 parts, separately for IV and SC administration: dose escalation (Part 1) and dose expansion (Part 2). It will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of Teclistamab administered to adult participants with relapsed or refractory multiple myeloma. The overall safety of the study drug will be assessed by physical examinations, Eastern Cooperative Oncology Group performance status, laboratory tests, vital signs, electrocardiograms, adverse event monitoring, and concomitant medication usage. Disease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days) and to confirm stringent complete response (sCR), complete response (CR), or relapse from CR. The end of study (study completion) is defined as 2 years after the last participant in Part 3 has received his or her initial dose of teclistamab. Study record NCT04557098 is Phase 2 part of this study and study record NCT03145181 is Phase 1 part of this study.

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• France
  • Pierre Benite cedex, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon-Sud
  • Tours, France, 37044
    • Recruiting
    • CHRU Tours Hopital Bretonneau
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VU Medisch Centrum
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Recruiting
    • Haematology Centre, R 51
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Measurable multiple myeloma that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory multiple myeloma or be intolerant of those established multiple myeloma therapies, and a candidate for Teclistamab treatment in the opinion of the treating physician. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory drug and anti-CD38 monoclonal antibody in any order during the course of treatment. Participants who could not tolerate a proteasome inhibitor or immunomodulatory drugs and an anti-CD38 monoclonal antibody are allowed
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Female participants of childbearing potential must use acceptable method of contraception
• Participants must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

• Prior treatment with any B cell maturation antigen (BCMA) targeted therapy
• Prior antitumor therapy as follows, before the first dose of study drug: Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less; Monoclonal antibody treatment for multiple myeloma within 21 days; Cytotoxic therapy within 21 days; Proteasome inhibitor therapy within 14 days; Immunomodulatory agent therapy within 7 days; Gene modified adoptive cell therapy (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months; Radiotherapy within 14 days or focal radiation within 7 days
• Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
• Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (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

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation (IV); Participants will receive Teclistamab intravenously (IV).	Drug: Teclistamab (IV); Participants will receive IV infusion of Teclistamab.; Other Names: JNJ-64007957
Experimental: Part 2: Dose Expansion (IV); Participants will receive Teclistamab IV.	Drug: Teclistamab (IV); Participants will receive IV infusion of Teclistamab.; Other Names: JNJ-64007957
Experimental: Part 1: Dose Escalation (SC); Participants will receive Teclistamab subcutaneously (SC).	Drug: Teclistamab(SC); Participants will receive SC injection of Teclistamab.; Other Names: JNJ-64007957
Experimental: Part 2: Dose Expansion (SC); Participants will receive Teclistamab SC.	Drug: Teclistamab(SC); Participants will receive SC injection of Teclistamab.; Other Names: JNJ-64007957

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Day 28
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 7 years and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Teclistamab Serum Concentrations	Concentration assessment will be done to evaluate the effect of Teclistamab.	Up to 8 weeks
Number of Participants with Teclistamab Antibodies	Antibodies to Teclistamab will be assessed to evaluate potential immunogenicity.	Up to 8 weeks
Preliminary Antitumor Activity of Teclistamab at the RP2D(s) in Part 2	Preliminary antitumor activity of Teclistamab will be done using the International Myeloma Working Group (IMWG) response criteria.	Up to End of Treatment (Approximately 91 days)
Biomarker Assessment	Biomarker assessment may be done to evaluate the effect of Teclistamab.	Up to 8 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393.
• 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.
• Girgis S, Lin SXW, Pillarisetti K, Banerjee A, Stephenson T, Ma X, Shetty S, Yang TY, Hilder BW, Jiao Q, Hanna B, Adams HC 3rd, Sun YN, Sharma A, Smit J, Infante JR, Goldberg JD, Elsayed Y. Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Target Oncol. 2022 Jul;17(4):433-439. doi: 10.1007/s11523-022-00893-y. Epub 2022 Jun 24. Erratum In: Target Oncol. 2022 Aug 1;:
• Usmani SZ, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Rosinol L, Chari A, Bhutani M, Karlin L, Benboubker L, Pei L, Verona R, Girgis S, Stephenson T, Elsayed Y, Infante J, Goldberg JD, Banerjee A, Mateos MV, Krishnan A. Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021 Aug 21;398(10301):665-674. doi: 10.1016/S0140-6736(21)01338-6. Epub 2021 Aug 10.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): November 9, 2021
• Study Completion (Estimated): July 22, 2026

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): April 25, 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; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Hematologic Neoplasms; Multiple Myeloma
• Other Study ID Numbers: CR108206; 2016-002122-36 (EudraCT Number); 64007957MMY1001 (Other Identifier: Janssen Research & Development, LLC); 2023-503438-40-00 (Registry Identifier: EUCT number)

Drug and device information, study documents

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