- |||||||||| Tecvayli (teclistamab-cqyv) / Genmab, J&J, Talvey (talquetamab-tgvs) / J&J
Trial primary completion date, Combination therapy: MonumenTAL-6: A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide (clinicaltrials.gov) - Apr 25, 2024
P3, N=795, Recruiting,
Primary resistance is characterized by a low T-cell/MM cell-ratio and Treg-driven immunosuppression, while reduced T-cell fitness due to continuous BsAb-mediated T-cell activation may contribute to development of acquired resistance. Trial primary completion date: Jun 2027 --> Apr 2026
- |||||||||| Review, Journal: Therapeutic progress in relapsed/refractory multiple myeloma. (Pubmed Central) - Apr 13, 2024
Additionally, novel antibody drugs, such as elotuzumab and selinexor, as well as bispecific antibodies, teclistamab and talquetamab, are currently undergoing clinical research with promising outcomes. However, chimeric antigen receptor-T cell therapy targeting B-cell maturation antigen remains the optimal approach for MM treatment.
- |||||||||| Darzalex (daratumumab) / J&J, Tecvayli (teclistamab-cqyv) / Genmab, J&J, Talvey (talquetamab-tgvs) / J&J
Review, Journal: Targeting GPRC5D in multiple myeloma. (Pubmed Central) - Apr 12, 2024
Additionally, ongoing trials examining talquetamab in combination with agents like daratumumab and teclistamab are discussed. We offer insights into the potential utilization of various GPRC5D based therapies in the treatment paradigm for MM, either independently or in combination with established therapies.
- |||||||||| Journal: A pivotal decade for bispecific antibodies? (Pubmed Central) - Mar 15, 2024
Notably, of the 13 currently approved bsAbs, two, emicizumab and faricimab, have achieved blockbuster status, showing the promise of this novel class of therapeutics. In the 2020s, the approval of additional bsAbs can be expected in hematological malignancies, solid tumors and non-oncology indications, establishing bsAbs as essential part of the therapeutic armamentarium.
- |||||||||| Talvey (talquetamab-tgvs) / J&J
Journal: Talquetamab (Pubmed Central) - Mar 9, 2024
In the 2020s, the approval of additional bsAbs can be expected in hematological malignancies, solid tumors and non-oncology indications, establishing bsAbs as essential part of the therapeutic armamentarium. No abstract available
- |||||||||| Tecvayli (teclistamab) / Genmab, J&J, Talvey (talquetamab) / J&J
SALVAGE SECOND AUTOLOGOUS STEM CELL TRANSPLANTS FOR PATIENTS WITH MYELOMA: A 24-YEAR RETROSPECTIVE AUDIT IN A NATIONAL TERTIARY REFERRAL CENTRE (1999-2022) (ePoster area) - Feb 14, 2024 - Abstract #EBMT2024EBMT_2509;
The pattern of patient referrals has been relatively conservative with a median time between autologous transplants of 55 months overall and 85 months in the most recent cohort (2017-2022). It is likely that the selection of lower risk patients who were more likely to have a durable response to repeated treatment with high dose melphalan and the more recent availability of novel therapies such as anti-CD38 antibodies and bispecific antibodies such as Teclistamab and Talquetamab are factors in the superior OS in patients transplanted since 2015.
- |||||||||| Tecvayli (teclistamab-cqyv) / Genmab, J&J, Talvey (talquetamab-tgvs) / J&J
Enrollment open, Combination therapy: MonumenTAL-6: A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide (clinicaltrials.gov) - Jan 31, 2024
P3, N=795, Recruiting,
It is likely that the selection of lower risk patients who were more likely to have a durable response to repeated treatment with high dose melphalan and the more recent availability of novel therapies such as anti-CD38 antibodies and bispecific antibodies such as Teclistamab and Talquetamab are factors in the superior OS in patients transplanted since 2015. Not yet recruiting --> Recruiting
- |||||||||| Tecvayli (teclistamab-cqyv) / Genmab, J&J, Talvey (talquetamab-tgvs) / J&J
New P3 trial, Combination therapy: MonumenTAL-6: A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortezomib, and Dexamethasone in Participants With Relapsed or Refractory Myeloma Who Have Received an Anti-CD38 Antibody and Lenalidomide (clinicaltrials.gov) - Jan 17, 2024
P3, N=795, Not yet recruiting,
- |||||||||| Elrexfio (elranatamab-bcmm) / Pfizer, Tecvayli (teclistamab) / Genmab, J&J, Talvey (talquetamab) / J&J
Journal: BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: Efficacy, safety and resistance mechanisms. (Pubmed Central) - Jan 9, 2024
Bispecific antibodies that engage T cells to target B cell maturation antigen (BCMA) or G protein-coupled receptor class C group 5 member D (GPRC5D) have demonstrated remarkable efficacy in heavily pretreated relapsed or refractory MM leading to the recent accelerated approval of teclistamab, elranatamab and talquetamab by health agencies. Future challenges however remain to define their optimal dosing schedule and duration, sequencing and integration with established anti-MM therapeutics as well as delineating the biological and clinical mediators of immune escape.
- |||||||||| Journal: Antibodies to watch in 2024. (Pubmed Central) - Jan 9, 2024
In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.
- |||||||||| Tecvayli (teclistamab) / Genmab, J&J, Talvey (talquetamab) / J&J
Phase classification, Combination therapy, Checkpoint inhibition: TRIMM-3: A Study of Talquetamab and Teclistamab Each in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - Dec 6, 2023
P1, N=152, Recruiting,
One of them is G protein-coupled receptor, class C group 5 member D (GPRC5D), that due to the very promising data from the use of chimeric Phase classification: P1b --> P1
- |||||||||| Immune and Genome Profiling of Myeloma Patients Treated with Sequential Immunotherapies Reveal Differential Non-Overlapping Mechanisms of Resistance ((Virtual Program)) - Nov 27, 2023 - Abstract #ASH2023ASH_6989;
Patient 3 received 3 sequential therapies with Ide-cel (DOR = 3 mos), teclistamab (DOR = 6 mos), and then talquetamab with daratumumab with an ongoing response of 11 mos...Patient 5 with penta-refractory disease and high disease burden (> 90% BM infiltration) had no response to elranatamab, however achieved an ongoing sCR (DOR = 30 mos) with talquetamab, daratumumab and pomalidomide (Tal-DP)...Therefore, TCE resistance derived from BCMA mutations does not preclude retreatment with another anti-BCMA TCE or CAR T. We here describe variable non-overlapping mechanisms mediating resistance to sequential TCE and CAR T therapies. Dynamic surveillance for antigenic escape and functional evaluation of T cell fitness will optimize immunotherapy sequencing.
- |||||||||| Review, Journal: Novel Immunotherapies and Combinations: The Future Landscape of Multiple Myeloma Treatment. (Pubmed Central) - Nov 25, 2023
In multiple myeloma impressive outcomes have improved with the introduction of new therapeutic approaches, mainly those including naked monoclonal antibodies such as daratumumab and isatuximab...Nevertheless, several issues regarding their use are unsolved, such as how to select patients for each strategy or how to sequence these therapies within the MM therapeutic landscape. Here we provide an overview of the most recent data about approved conjugated monoclonal antibody belantamab, mafodotin, bispecific antibody teclistamab, and other promising compounds under development, mainly focusing on the ongoing clinical trials with monoclonal antibody combination approaches in advanced and earlier phases of MM treatment.
- |||||||||| Tecvayli (teclistamab) / Genmab, J&J, Talvey (talquetamab) / J&J
Phase classification: RedirecTT-1: A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - Nov 22, 2023
P1/2, N=164, Recruiting,
Here we provide an overview of the most recent data about approved conjugated monoclonal antibody belantamab, mafodotin, bispecific antibody teclistamab, and other promising compounds under development, mainly focusing on the ongoing clinical trials with monoclonal antibody combination approaches in advanced and earlier phases of MM treatment. Phase classification: P1b/2 --> P1/2
- |||||||||| Review, Journal: Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future. (Pubmed Central) - Nov 18, 2023
This has been driven largely by the introduction of new classes of small molecules, such as proteasome blockers (e.g., bortezomib) and immunomodulators (e.g., lenalidomide), as well as by immunotherapeutic agents starting with the anti-CD38 monoclonal antibody daratumumab in 2015...These include the bispecifics teclistamab, talquetamab, and elranatamab, and the chimeric antigen receptor (CAR) T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel)...Included in the discussion are additional monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bi- and multitargeted mAbs, and CAR T-cells and emerging natural killer (NK) cells, including products intended for "off-the-shelf" (allogeneic) applications. Emphasis is placed on the benefits of each along with the challenges that need to be surmounted if MM is to be cured.
- |||||||||| Tecvayli (teclistamab-cqyv) / Genmab, J&J, Darzalex Faspro (daratumumab/hyaluronidase) / J&J, Talvey (talquetamab-tgvs) / J&J
Enrollment open, Trial completion date, Trial primary completion date, Combination therapy, Immuno-oncology: Teclistamab or Talquetamab in Combination With Daratumumab for High-Risk Smoldering Myeloma (REVIVE Study) (clinicaltrials.gov) - Nov 13, 2023
P2, N=50, Recruiting,
Emphasis is placed on the benefits of each along with the challenges that need to be surmounted if MM is to be cured. Not yet recruiting --> Recruiting | Trial completion date: Aug 2029 --> Dec 2029 | Trial primary completion date: Aug 2028 --> Dec 2028
- |||||||||| Elrexfio (elranatamab-bcmm) / Pfizer, Tecvayli (teclistamab) / Genmab, J&J, Talvey (talquetamab) / J&J
FDA event, Journal: An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. (Pubmed Central) - Nov 3, 2023
In the past year, three new bispecific antibodies have received accelerated FDA approval for the treatment of relapsed/refractory multiple myeloma. In this article, we review the available data for these three agents, teclistamab, elranatamab, and talquetamab, and discuss practical considerations for their use in clinical settings while the medical community awaits randomized phase III clinical trial datasets comparing them to standard-of-care regimens.
- |||||||||| Talvey (talquetamab) / J&J
Updated Results of Talquetamab, a GPRC5D (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4318;
P1, P2
Among the 229 patients included, 200 (87%) received an anti-BCMA BsAb with teclistamab (n=153, These updated results from pts with prior TCR in the phase 1/2 MonumenTAL-1 study show continued strong efficacy of GPRC5D-targeting talquetamab across populations exposed to TCR (predominantly anti-BCMA), with notable ORR of 73% and mDOR of >1 year in the post
- |||||||||| Pooled Analysis on Bispecific Antibody-Related Toxicities in Multiple Myeloma (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_2383;
Our results showed that non-BCMA bsAb were associated less hematotoxicity (combined grade 3-4 events and hypogammaglobulinemia), whereas BCMA bsAb were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes.
- |||||||||| Immune and Genome Profiling of Myeloma Patients Treated with Sequential Immunotherapies Reveal Differential Non-Overlapping Mechanisms of Resistance (Halls G-H (San Diego Convention Center)) - Nov 3, 2023 - Abstract #ASH2023ASH_2374;
Patient 3 received 3 sequential therapies with Ide-cel (DOR = 3 mos), teclistamab (DOR = 6 mos), and then talquetamab with daratumumab with an ongoing response of 11 mos...Patient 5 with penta-refractory disease and high disease burden (> 90% BM infiltration) had no response to elranatamab, however achieved an ongoing sCR (DOR = 30 mos) with talquetamab, daratumumab and pomalidomide (Tal-DP)...Therefore, TCE resistance derived from BCMA mutations does not preclude retreatment with another anti-BCMA TCE or CAR T. We here describe variable non-overlapping mechanisms mediating resistance to sequential TCE and CAR T therapies. Dynamic surveillance for antigenic escape and functional evaluation of T cell fitness will optimize immunotherapy sequencing.
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