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

• ClinicalTrials.gov Identifier: NCT03145181
• Recruitment Status: Recruiting
• First Posted: May 9, 2017
• Last Update Posted: March 24, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hematological Malignancies	Drug: Teclistamab (IV); Drug: Teclistamab(SC)	Phase 1

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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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 282 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 16, 2017
• Actual Primary Completion Date: November 9, 2021
• Estimated Study Completion Date: January 23, 2025

Arms and Interventions

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 Name: JNJ-64007957
Experimental: Part 2: Dose Expansion (IV); Participants will receive Teclistamab IV.	Drug: Teclistamab (IV); Participants will receive IV infusion of Teclistamab.; Other Name: 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 Name: JNJ-64007957
Experimental: Part 2: Dose Expansion (SC); Participants will receive Teclistamab SC.	Drug: Teclistamab(SC); Participants will receive SC injection of Teclistamab.; Other Name: JNJ-64007957

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]
   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.
2. Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 7 years and 3 months ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

United States, New York

Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects; Recruiting

New York, New York, United States, 10029

United States, North Carolina

Levine Cancer Institute; Recruiting

Charlotte, North Carolina, United States, 28204

United States, Pennsylvania

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

France

Centre hospitalier Lyon-Sud; Recruiting

Pierre Benite cedex, France, 69495

CHRU Tours Hôpital Bretonneau; Recruiting

Tours, France, 37044

Netherlands

VU Medisch Centrum; Recruiting

Amsterdam, Netherlands, 1081 HV

Spain

Hosp. Univ. Germans Trias I Pujol; Recruiting

Badalona, Spain, 08916

Hosp. Clinic I Provincial de Barcelona; Recruiting

Barcelona, Spain, 08036

Clinica Univ. de Navarra; Recruiting

Pamplona, Spain, 31008

Hosp. Clinico Univ. de Salamanca; Recruiting

Salamanca, Spain, 37007

Sweden

Haematology Centre, R 51; Recruiting

Stockholm, Sweden, SE-141 86

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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;:

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.

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.

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.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03145181
• Other Study ID Numbers: CR108206; 2016-002122-36 ( EudraCT Number ); 64007957MMY1001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: May 9, 2017
• Last Update Posted: March 24, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Hematologic Neoplasms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site