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DRUG:

cevostamab (RG6160)

i
Other names: RG6160, BFCR 4350A, RG 6160, BFCR4350A, RO-7187797, RO7187797, BFCR-4350A, RG-6160, RO 7187797
Associations
Trials
Company:
Roche
Drug class:
CD3 agonist, FCRH5 inhibitor
Related drugs:
Associations
Trials
8d
Cevostamab in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study Demonstrate Clinically Meaningful Activity and Manageable Safety and Inform the Doses and Regimen for Combination Studies (ASH 2024)
P1 | "Pts with CRS were managed with tocilizumab (47.4%), steroids (21.1%), or both agents (10.5%). Cevostamab demonstrates clinically meaningful activity and manageable safety at the 160mg TD level in pts with heavily pretreated RRMM. C1 TS dosing provides effective CRS mitigation. Cevostamab combination studies may use the 0.3/1.2/3.6mg TS regimen and the Q3W 160mg TD (or similar TD exposure)."
P1 data • Clinical
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Actemra IV (tocilizumab) • cevostamab (RG6160)
27d
CAMMA 1: A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P1, N=184, Recruiting, Genentech, Inc. | Trial completion date: Jul 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Jan 2026
Trial completion date • Trial primary completion date
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Darzalex (daratumumab) • dexamethasone • pomalidomide • Actemra IV (tocilizumab) • cevostamab (RG6160)
6ms
IL-15/IL-15Rα-Fc fusion protein XmAb24306 potentiates activity of CD3 bispecific antibodies through enhancing T cell expansion. (PubMed, Mol Cancer Ther)
Activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in upregulation of IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to the IL-15. In summary, our results support the hypothesis where the number of tumor infiltrating T cells is rate limiting for the activity of solid tumor targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T cell bispecific antibodies supports clinical evaluation of this novel immunotherapy combination.
Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL2 (Interleukin 2) • IL15 (Interleukin 15)
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cevostamab (RG6160)
9ms
Enrollment change
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Actemra IV (tocilizumab) • cevostamab (RG6160)
1year
Evaluation of Immune Reconstitution in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Cevostamab in Phase I Study GO39775 (ASH 2023)
At data cut-off (March 1, 2023), a total of 310 patients were enrolled in GO39775. 76 patients met the inclusion criteria and were eligible for analysis. Median age was 65 years (range: 43–82), with a median of 6 previous lines of therapy (range: 2–12).
Clinical • P1 data
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cevostamab (RG6160)
1year
High Dimensional Profiling of Patient-Derived Multiple Myeloma Bone Marrow Specimens Treated with an FcRH5-Targeted Bispecific Ex Vivo (ASH 2023)
Background: Cevostamab is an FcRH5 (Fc receptor-homolog 5) targeted T cell-dependent bispecific (TDB) currently being evaluated in the clinic, with promising activity and favorable safety profile as a monotherapy in patients (pts) with heavily pre-treated Relapsed/Refractory multiple myeloma (MM) (NCT03275103, Trudel et al... We first examined the T cell compartment by scRNA-seq profiling. Upon FcRH5 TDB treatment, clustering analysis suggested that CD4 and CD8 T cells undergo extensive transcriptional changes compared to control TDB (Fig 1A). A TNF and LTA-expressing CD4 memory cluster was enriched upon treatment in both SoRs and Rs, but to a greater extent in Rs.
Preclinical • IO biomarker
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CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CD44 (CD44 Molecule) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • SDC1 (Syndecan 1) • CCND2 (Cyclin D2) • HLA-E (Major Histocompatibility Complex, Class I, E) • SOCS1 (Suppressor Of Cytokine Signaling 1) • TNFSF10 (TNF Superfamily Member 10)
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CD44 expression • CXCL9 expression • CD4 expression
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cevostamab (RG6160)
1year
Sequential T-Cell Engagement for Myeloma ("STEM") Trial: A Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy (ASH 2023)
Background and significance: The BCMA-targeted CAR T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are currently approved for relapsed/refractory multiple myeloma (RRMM) patients with ≥4 prior lines of therapy, including an IMID, proteasome inhibitor, and CD38 antibody. This phase 2 study is exploring the efficacy, safety, and feasibility of cevostamab consolidation following BCMA-directed CAR T cell therapy for RRMM, with the goal of sequential T cell engagement against 2 different antigens to eliminate residual disease. Accrual started in July 2023.
CAR T-Cell Therapy • P2 data • IO biomarker
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clonoSEQ
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Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • cevostamab (RG6160)
1year
Integrative Analysis of the Tumor and Microenvironment to Model the Molecular Heterogeneity Underlying the Response to Cevostamab in Relapsed/Refractory Multiple Myeloma (ASH 2023)
Patients who had less than 25% missingness in any data layer were selected from the single-step (3.6/90–252mg dose levels [n=49] and 3.6/90mg tocilizumab premedication group [n=14; Trudel et al. Our novel, unbiased, machine learning, integrative clustering approach not only revealed unique molecular subtypes that illustrate the heterogeneity of patients with RRMM, but also identified immunological features associated with potentially reduced response to cevostamab therapy, which could provide direction for future research.
Actemra IV (tocilizumab) • cevostamab (RG6160)
over1year
Bispecific antibodies targeting BCMA, GPRC5D, and FcRH5 for multiple myeloma therapy: latest updates from ASCO 2023 Annual Meeting. (PubMed, J Hematol Oncol)
Teclistamab was approved for relapsed/refractory MM therapy in 2022, while elranatamab, linvoseltamab, F182112, talquetamab, and cevostamab are currently undergoing clinical trials. This study summarizes several latest reports on bsAbs for the treatment of MM from the ASCO 2023 Annual Meeting.
Journal
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Elrexfio (elranatamab-bcmm) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv) • F182112 • cevostamab (RG6160) • linvoseltamab (REGN5458)
over1year
T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA. (PubMed, Curr Opin Oncol)
Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.
Journal • Trispecific
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Talvey (talquetamab-tgvs) • cevostamab (RG6160) • forimtamig (RG6234)
over1year
Cevostamab Following CAR T Cell Therapy for RRMM (clinicaltrials.gov)
P2, N=30, Recruiting, University of Pennsylvania | Not yet recruiting --> Recruiting
Enrollment open • CAR T-Cell Therapy
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cevostamab (RG6160)
over1year
New P1 trial
|
Elrexfio (elranatamab-bcmm) • Actemra IV (tocilizumab) • cevostamab (RG6160)
over1year
MODULE 1: Multiple Myeloma (MM) (ASCO 2023)
This activity is supported by educational grants from AbbVie Inc, Genentech, a member of the Roche Group, Genmab US Inc, Karyopharm Therapeutics, Lilly, Regeneron Pharmaceuticals Inc, Sanofi, and Seagen Inc. Clinical and biological factors affecting the selection of up-front therapy for patients with MMLong-term findings with daratumumab-containing regimens for newly diagnosed MM; role for transplant-eligible and ineligible patientsPublished data with novel daratumumab-based quadruplet regimens for transplant-eligible patients with newly diagnosed MMSimilarities and differences between daratumumab and isatuximabKey findings from the Phase III GMMG HD7 trial comparing isatuximab with RVd to RVd alone for transplant-eligible patients with newly diagnosed MMOngoing Phase III studies of isatuximab as a part of induction therapy for transplant-eligible and ineligible patientsAvailable data with and current role of minimal residual disease assessment in therapeutic decision-makingOptimal maintenance approach for transplant-eligible and ineligible patientsResults from Phase III trials evaluating isatuximab-based combination regimens for relapsed/refractory (R/R) MMKey results from the Phase III BOSTON trial leading to the FDA approval of selinexor in combination with bortezomib/dexamethasone for R/R MM; available data with other selinexor-based combinationsStructural makeup and manufacturing of available B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell platformsEfficacy and safety findings from the KarMMa (idecabtagene vicleucel) and CARTITUDE-1 (ciltacabtagene autoleucel) trials for R/R MMAvailable and emerging data with and ongoing studies of BCMA-targeted CAR T-cell therapies in earlier lines of treatmentSimilarities and differences in the cellular targets and mechanisms of action of bispecific antibodies in MMActivity and responses observed with available (teclistamab) and investigational (elranatamab, linvoseltamab, ABBV-383) BCMA-targeted bispecific antibodies in R/R MMBiological rationale for and available data with non-BCMA-targeted bispecific antibodies (eg, talquetamab, cevostamab, forimtamig); FDA breakthrough therapy designation for talquetamabSpectrum, incidence and severity of toxicities, including cytokine release syndrome and neurotoxicity, with bispecific antibodies in patients with MM; mitigation and management protocolsPublished data with and current role of venetoclax-based therapy for patients with MM and t(11;14) or Bcl-2 overexpressionOther promising novel strategies in clinical development for patients with MM
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2)
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Chr t(11;14) • BCL2 overexpression
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Venclexta (venetoclax) • bortezomib • Xpovio (selinexor) • Darzalex (daratumumab) • dexamethasone • Sarclisa (isatuximab-irfc) • Elrexfio (elranatamab-bcmm) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv) • ABBV-383 IV • cevostamab (RG6160) • forimtamig (RG6234) • linvoseltamab (REGN5458)
over1year
INFECTIONS FOLLOWING BISPECIFIC ANTIBODIES IN MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2023)
Despite promising efficacy in MM, BsAbs may come with substantial infection risk, warranting more detailed analysis of infections and immune phenotyping to guide targeted supportive care. Table – Summary of included studiesAgent Target Source Phase Enrolment (mm/yy) N Median prior lines All- Grade Infection N (%) Grade ≥3 Infection N (%) Alnuctamab (CC-93269) BCMA Wong 2022 I 03/18- 68 4 23 (34) 6 (9) ABBV-383 BCMA Voorhees 2022 I 10/22- 174 5 61/124 (50) 39/124 (22) Elranatamab BCMA Raje 2022 I 10/21- 123 5 82 (67) 43 (35) Linvoseltamab (REGN545) BCMA Bumma 2022 Ib/II 1/19- 252 5 136 (54) 73 (29) Pacanalotamab (AMG-420) BCMA Topp 2020 I 3/19 – 4/22 42 5 14 (33) 10 (24) Teclistamab BCMA Moreau 2022 I/II 09/20- 165 5 126 (77) 57 (45) Teclistamab + daratumumab BCMA + CD38 Rodriguez- Otero 2022 II 03/21- 46 5 29 (63) 8 (17) Forimtamig (RG6234) GPRC5D Carlo- Stella 2022 I 11/20- IV: 51 SC: 57 IV: 5 SC: 4 IV: 31 (61) SC: 26 (46) IV:11 (22) SC:15 (27) Talquetamab GPRC5D Chari 2022 I/II 02/21- 288 5 153 (53) 46 (16) Talquetamab + daratumumab GPRC5D + CD38 Van de Donk 2022 II 09/21- 46 5 23 (50) 6 (13) Cevostamab (BFCR4350A) FcRH5 Trudel 2021 I 07/21- 161 6 68 (43) 18 (11) Bispecific, Multiple myeloma, Cellular therapy
Retrospective data • Review
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Darzalex (daratumumab) • Elrexfio (elranatamab-bcmm) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv) • alnuctamab (CC-93269) • ABBV-383 IV • cevostamab (RG6160) • forimtamig (RG6234) • linvoseltamab (REGN5458) • pacanalotamab (AMG 420)
over1year
TOCILIZUMAB PRE-TREATMENT SIGNIFICANTLY REDUCES THE INCIDENCE OF CYTOKINE RELEASE SYNDROME IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) WHO RECEIVE CEVOSTAMAB (EHA 2023)
TCZ pre-treatment significantly reduces the incidence of CRS in pts with RRMM who receive cevostamab. Importantly, TCZ pre-treatment has no negative impact on the anti-myeloma activity of cevostamab. Cytokine release syndrome, Antibody, Bispecific, Multiple myeloma
Clinical
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IL6 (Interleukin 6) • CRP (C-reactive protein)
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Actemra IV (tocilizumab) • cevostamab (RG6160)
over1year
Trial completion date
|
Darzalex (daratumumab) • dexamethasone • pomalidomide • Actemra IV (tocilizumab) • cevostamab (RG6160)
over1year
Enrollment change
|
lenalidomide • Actemra IV (tocilizumab) • cevostamab (RG6160)
over1year
CAMMA 2: A phase I/II trial evaluating the efficacy and safety of cevostamab in patients with relapsed/refractory multiple myeloma (RRMM) who have triple-class refractory disease and have received a prior anti-B-cell maturation antigen (BCMA) agent. (ASCO 2023)
CRS is managed per protocol based on the clinical presentation and may involve corticosteroid and tocilizumab treatment. As of February 2023, enrolment into Cohorts A1 and A2 is ongoing. Clinical trial information: NCT05535244.
P1/2 data • Clinical
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Actemra IV (tocilizumab) • cevostamab (RG6160)
2years
Pretreatment with Tocilizumab Prior to the CD3 Bispecific Cevostamab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Showed a Marked Reduction in Cytokine Release Syndrome Incidence and Severity (ASH 2022)
Pts in both arms received corticosteroid, antihistamine and acetaminophen premedication prior to cevostamab. Clinical data from the GO39775 study shows for the first time that TCZ pretreatment can significantly reduce the risk of developing TDB-induced CRS without an apparent impact on anti-myeloma activity. The data support additional investigation of the use of anti-cytokine pretreatment with the goal of substantially reducing the frequency and potentially the severity of CRS.
Clinical
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CRP (C-reactive protein)
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Actemra IV (tocilizumab) • cevostamab (RG6160)
2years
Enduring Responses after 1-Year, Fixed-Duration Cevostamab Therapy in Patients with Relapsed/Refractory Multiple Myeloma: Early Experience from a Phase I Study (ASH 2022)
Early data from this Phase I study suggest that patients can maintain durable responses (≥6 months) after completion of 17 cycles of cevostamab treatment, highlighting the potential for an extended treatment-free period following fixed-duration therapy. Further data are needed to confirm the duration of response and associated correlates following completion of treatment. Additional data on responding patients with premature discontinuation of treatment (i.e.
P1 data • Clinical
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cevostamab (RG6160)
3years
[VIRTUAL] Early pharmacodynamic changes in T-cell activation, proliferation, and cytokine production in patients with relapsed/refractory multiple myeloma (RRMM) treated with cevostamab (anti-FcRH5xCD3) (BLOOD 2021)
Results confirm the mechanism of action of cevostomab and support C1 step-up dosing for CRS mitigation in RRMM. Early data suggest that higher peripheral CD8 T-cell expansion and TILs were detected, at the end of C1, in responders than in non-responders.
Clinical • PK/PD data
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CD8 (cluster of differentiation 8)
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cevostamab (RG6160)