Clinical trial NCT04557098: A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1/2, 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hematological Malignancies
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose (RP2D).


Eligibility criteria: Inclusion Criteria: -

* Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
* Measurable disease: Cohort A and Cohort C: Multiple myeloma must be measurable by central laboratory assessment
* A female participant of childbearing potential must have a negative pregnancy test at screening
* Willing and able to adhere to the prohibitions and restrictions specified in this protocol
* Cohort A: received at least \>=3 prior lines of therapy and previously received a PI, an IMiD and an anti-CD38 monoclonal antibody; Cohort C: received \>= 3 prior lines of therapy that included a PI, an IMiD, an anti-CD38 monoclonal antibody, and an anti-B cell maturation antigen (BCMA) treatment (with CART-T cells or an antibody drug conjugate (ADC)

Exclusion Criteria:

* Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light-chain amyloidosis
* The following medical conditions: Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation, human immunodeficiency virus (HIV) infection, hepatitis B or C infection, stroke or seizure less than or equal to (\<=) 6 m, autoimmune disease, uncontrolled systemic infection, cardiac conditions (Myocardial Infarction \<= 6 m, stage III-IV congestive heart failure, etc)
* Received any therapy that is targeted to BCMA, with the exception of Cohort C in Part 3
* Prior antitumor therapy, within 21 days (PI or radiotherapy within 14 days, IMiDs within 7 days, Gene modified adoptive cell therapy within 3 months) prior to first dose of study drug
* Toxicities from previous anticancer therapies that have not resolved to baseline or to \<= grade 1 (except for alopecia or peripheral neuropathy)
* Received a cumulative dose of corticosteroids equivalent to \>=140 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 (MM)
* Myelodysplastic syndrome or active malignancies other than relapsed/refractory multiple myeloma with exceptions are: 1) Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured 2) Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. 3) Noninvasive cervical cancer treated within the last 24 months that is considered completely cured. 4) Localized prostate cancer (N0M0) 5) Breast cancer: Adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. 6) Malignancy that is considered cured with minimal risk of recurrence
* Prior allogenic stem cell transplant \<=6 months
* Prior autologous stem cell transplant \<=12 weeks
* Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab

Primary outcomes:
measure: Cohorts A and C: Overall Response Rate (ORR)
timeFrame: Up to 2.9 years
Secondary outcomes:
measure: Cohorts A and C: Duration of Response (DOR)
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Very Good Partial Response (VGPR) or Better Rate
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Cohorts A and C: Complete Response (CR) or Better Rate
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Stringent Complete Response (sCR) Rate
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Time to Response (TTR)
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Progression-free Survival (PFS)
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Overall Survival (OS)
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Minimal Residual Disease (MRD) Negative Rate
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Number of Participants with AEs by Severity
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Serum Concentration of Teclistamab
timeFrame: Up to 3 months
measure: Cohorts A and C: Number of Participants with Teclistamab Antibodies
timeFrame: Up to 2.9 years
measure: Cohorts A and C: Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30)
timeFrame: Baseline, up to 2.9 years
measure: Cohorts A and C: Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)
timeFrame: Baseline, up to 2.9 years
measure: Cohorts A and C: Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)
timeFrame: Baseline, up to 2.9 years
measure: Cohorts A and C: Overall Response Rate (ORR) in Participants with High-risk Molecular Features
timeFrame: Up to 2.9 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute Emory University
state: Georgia
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - UZ GENT
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network UHN Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Beijing
country: China
facility: Peking University First Hospital
city: Chengdu
country: China
facility: West China Hospital Si Chuan University
city: Guangzhou
country: China
facility: Sun Yat -Sen University Cancer Center
city: Hangzhou
country: China
facility: First affiliated Hospital of Zhejiang University
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
city: Lille Cedex
country: France
facility: Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
city: Nantes
country: France
facility: C.H.U. Hotel Dieu - France
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHRU Hôpital Jean Bernard
city: Toulouse cedex 9
country: France
facility: Pôle IUC Oncopole CHU
city: Tours
country: France
facility: CHRU Hôpital Bretonneau
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Skane University Hospital
city: Stockholm
country: Sweden
facility: Haematology Centre, R 51
city: London
country: United Kingdom
facility: University College Hospital
city: Sothampton
country: United Kingdom
facility: University Hospital Southampton
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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.