Abstract
Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM).
Author
person
Cyrille Touzeau
Centre Hospitalier Universitaire de Nantes, Nantes, France
info_outline
Cyrille Touzeau, Meral Beksac, Evangelos Terpos, Saad Zafar Usmani, Amrita Y. Krishnan, Inger S. Nijhof, Wojciech Janowski, Cyrille Hulin, Sebastian Grosicki, Michel Delforge, Dana McAleer, Sarah Nagle, Yunsi Olyslager, Jonathan Miller, Zoe Craig, Josephine Khan, Tobias Kampfenkel, Salomon Manier, Niels W.C.J. van de Donk
Full text
Authors
person
Cyrille Touzeau
Centre Hospitalier Universitaire de Nantes, Nantes, France
info_outline
Cyrille Touzeau, Meral Beksac, Evangelos Terpos, Saad Zafar Usmani, Amrita Y. Krishnan, Inger S. Nijhof, Wojciech Janowski, Cyrille Hulin, Sebastian Grosicki, Michel Delforge, Dana McAleer, Sarah Nagle, Yunsi Olyslager, Jonathan Miller, Zoe Craig, Josephine Khan, Tobias Kampfenkel, Salomon Manier, Niels W.C.J. van de Donk
Organizations
Centre Hospitalier Universitaire de Nantes, Nantes, France, Ankara University, Ankara, Turkey, University of Athens, School of Medicine, Athens, Greece, Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, City of Hope Comprehensive Cancer Center, Duarte, CA, St. Antonius Hospital, Nieuwegein, Netherlands, Calvary Mater Newcastle, New South Wales, Australia, Hôpital Haut Leveque, University Hospital, Pessac, France, Medical University of Silesia, Katowice, Poland, University of Leuven, Leuven, Belgium, Johnson & Johnson Innovative Medicine Research & Development, Spring House, PA, Johnson & Johnson Innovative Medicine Research & Development, Beerse, Belgium, Johnson & Johnson Innovative Medicine Research & Development, San Francisco, CA, Johnson & Johnson Innovative Medicine Research & Development, High Wycombe, United Kingdom, Johnson & Johnson Innovative Medicine Research & Development, Neuss, Germany, Lille University Hospital, Lille, France, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
Abstract Disclosures
Research Funding
Johnson & Johnson Innovative Medicine
Background:
Despite recent advances in the treatment (tx) of transplant ineligible/not intended NDMM, most pts still relapse and require alternative txs, highlighting a need for new frontline tx options with new mechanisms of action to improve pt outcomes. Teclistamab (tec) demonstrated rapid, deep, and durable responses in the MajesTEC-1 trial (NCT03145181/NCT04557098). Preliminary data from the MajesTEC-2 trial (NCT04722146) demonstrated that tec, daratumumab (dara), and lenalidomide (len) combination (tec + DR) is tolerable, with promising efficacy in pts with relapsed/refractory MM and NDMM. The phase 3 MajesTEC-7 (NCT05552222) study will compare tec + DR vs DR + dexamethasone (dex) in pts with NDMM who are ineligible/not intended for ASCT as initial tx. We report the results of the first safety run-in (SRI) from MajesTEC-7.
Methods:
Eligible patients were aged ≥18 yrs with NDMM and ineligible/not intended for ASCT as initial tx, with measurable disease and an ECOG performance status (PS) score 0–2. Pts in the SRI received tec (step-up dose [cycle 1], QW [cycle 2], Q2W [cycle 3–6], and Q4W [cycle 7+]) + DR (as SOC) until progression, unacceptable toxicity, or death. Response assessments were based on IMWG criteria. Adverse events (AEs) were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT criteria. Prophylactic immunoglobulin replacement was highly recommended.
Results:
As of Nov 27, 2023, 26 pts had received tec + DR (median, 11 cycles; range, 2–14) and 24 pts (92.3%) remained on tx. Median follow-up was 10.2 mo (range, 2–12). At baseline, median age was 72.5 yrs, 11.5% had an ECOG PS score of 2, and 15.4% had ≥1 soft-tissue plasmacytoma. 4 pts (15.4%) deferred transplant. Treatment-emergent AEs (TEAEs) occurred in 100% of pts (grade [gr] 3/4, 22 pts [84.6%]). Infections occurred in 25 pts (96.2%; gr 3/4, 8 pts [30.8%]). CRS occurred in 16 pts (61.5%; all gr 1). ICANS occurred in 1 pt (gr 1). Gr 3/4 TEAEs occurring in ≥3 pts were neutropenia (13 [50%]), febrile neutropenia (5 [19.2%]), thrombocytopenia (4 [15.4%]), COVID-19 (3 [11.5%]), maculo-papular rash (3 [11.5%]), and hypertension (3 [11.5%]). 1 pt discontinued tec + DR due to withdrawal of consent. 2 discontinued len due to TEAEs (gr 3 maculo-papular rash and gr 4 neutropenia). There was 1 death due to a TEAE in cycle 3 (pneumonia influenza). Overall response rate was 92.3% (complete response or better, 73.1%; very good partial response or better, 92.3%).
Conclusions:
These results from the first SRI of MajesTEC-7 demonstrate a manageable safety profile with early efficacy of tec + DR in NDMM. Two additional SRIs are ongoing investigating tec (less frequent dosing) + DR and talquetamab + DR. Clinical trial information: NCT05552222.
Clinical status
Clinical
1 clinical trial
23 organizations
1 product
4 drugs
5 targets
Organization
Centre Hospitalier Universitaire de NantesOrganization
Ankara UniversityOrganization
University of AthensOrganization
School of Medicine, Showa UniversityOrganization
Memorial Sloan Kettering Cancer CenterOrganization
City of Hope Comprehensive Cancer CenterOrganization
St. Antonius HospitalOrganization
Calvary Mater NewcastleOrganization
University Hospital 12 de OctubreOrganization
Medical University of SilesiaOrganization
University of LeuvenOrganization
Lille University HospitalOrganization
Vrije Universiteit AmsterdamOrganization
Johnson & Johnson Innovative Medicine Research & Development, High Wycombe, United KingdomOrganization
Myeloma ServiceDrug
TeclistamabDrug
daratumumabDrug
lenalidomideDrug
dexamethasoneProduct
talquetamabTarget
lenalidomideTarget
TeclistamabTarget
DexamethasoneTarget
talquetamabTarget
CD38Clinical trial
A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab SC and Lenalidomide (Tal-DR) Versus Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma Who Are Either Ineligible or Not Intended for Autologous Stem Cell Transplant as Initial TherapyStatus: Recruiting, Estimated PCD: 2031-04-30