Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)
Primary Purpose
Hematological Malignancies
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Teclistamab (IV)
Teclistamab(SC)
Sponsored by
About this trial
This is an interventional treatment trial for Hematological Malignancies
Eligibility 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
Sites / Locations
- City of HopeRecruiting
- Colorado Blood Cancer InstituteRecruiting
- Icahn School of Medicine at Mount Sinai Program for the Protection of Human SubjectsRecruiting
- Levine Cancer InstituteRecruiting
- University of PennsylvaniaRecruiting
- Centre hospitalier Lyon-SudRecruiting
- CHRU Tours Hôpital BretonneauRecruiting
- VU Medisch CentrumRecruiting
- Hosp. Univ. Germans Trias I PujolRecruiting
- Hosp. Clinic I Provincial de BarcelonaRecruiting
- Clinica Univ. de NavarraRecruiting
- Hosp. Clinico Univ. de SalamancaRecruiting
- Haematology Centre, R 51Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part 1: Dose Escalation (IV)
Part 2: Dose Expansion (IV)
Part 1: Dose Escalation (SC)
Part 2: Dose Expansion (SC)
Arm Description
Participants will receive Teclistamab intravenously (IV).
Participants will receive Teclistamab IV.
Participants will receive Teclistamab subcutaneously (SC).
Participants will receive Teclistamab SC.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Teclistamab Serum Concentrations
Concentration assessment will be done to evaluate the effect of Teclistamab.
Number of Participants with Teclistamab Antibodies
Antibodies to Teclistamab will be assessed to evaluate potential immunogenicity.
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.
Biomarker Assessment
Biomarker assessment may be done to evaluate the effect of Teclistamab.
Full Information
NCT ID
NCT03145181
First Posted
April 28, 2017
Last Updated
October 11, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT03145181
Brief Title
Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma
Acronym
MajesTEC-1
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 16, 2017 (Actual)
Primary Completion Date
November 9, 2021 (Actual)
Study Completion Date
September 27, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
282 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Dose Escalation (IV)
Arm Type
Experimental
Arm Description
Participants will receive Teclistamab intravenously (IV).
Arm Title
Part 2: Dose Expansion (IV)
Arm Type
Experimental
Arm Description
Participants will receive Teclistamab IV.
Arm Title
Part 1: Dose Escalation (SC)
Arm Type
Experimental
Arm Description
Participants will receive Teclistamab subcutaneously (SC).
Arm Title
Part 2: Dose Expansion (SC)
Arm Type
Experimental
Arm Description
Participants will receive Teclistamab SC.
Intervention Type
Drug
Intervention Name(s)
Teclistamab (IV)
Other Intervention Name(s)
JNJ-64007957
Intervention Description
Participants will receive IV infusion of Teclistamab.
Intervention Type
Drug
Intervention Name(s)
Teclistamab(SC)
Other Intervention Name(s)
JNJ-64007957
Intervention Description
Participants will receive SC injection of Teclistamab.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT)
Description
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.
Time Frame
Up to Day 28
Title
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Description
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.
Time Frame
Up to 7 years and 3 months
Secondary Outcome Measure Information:
Title
Teclistamab Serum Concentrations
Description
Concentration assessment will be done to evaluate the effect of Teclistamab.
Time Frame
Up to 8 weeks
Title
Number of Participants with Teclistamab Antibodies
Description
Antibodies to Teclistamab will be assessed to evaluate potential immunogenicity.
Time Frame
Up to 8 weeks
Title
Preliminary Antitumor Activity of Teclistamab at the RP2D(s) in Part 2
Description
Preliminary antitumor activity of Teclistamab will be done using the International Myeloma Working Group (IMWG) response criteria.
Time Frame
Up to End of Treatment (Approximately 91 days)
Title
Biomarker Assessment
Description
Biomarker assessment may be done to evaluate the effect of Teclistamab.
Time Frame
Up to 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Centre hospitalier Lyon-Sud
City
Pierre Benite cedex
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Name
CHRU Tours Hôpital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Recruiting
Facility Name
VU Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Hosp. Univ. Germans Trias I Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hosp. Clinic I Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Univ. de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hosp. Clinico Univ. de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Haematology Centre, R 51
City
Stockholm
ZIP/Postal Code
SE-141 86
Country
Sweden
Individual Site Status
Recruiting
12. IPD Sharing Statement
Citations:
PubMed Identifier
35749004
Citation
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;:
Results Reference
derived
PubMed Identifier
35661166
Citation
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.
Results Reference
derived
PubMed Identifier
34388396
Citation
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.
Results Reference
derived
PubMed Identifier
32956453
Citation
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.
Results Reference
derived
Links:
URL
https://clinicaltrials.gov/ct2/show/NCT04557098
Description
A Study of Teclistamab, in Participants With Relapsed or Refractory Multiple Myeloma
Learn more about this trial
Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma
We'll reach out to this number within 24 hrs