- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche
Early Experience with Mosunetuzumab and Managing Cytokine Release Syndrome: Results of a Single Center Retrospective (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_4492;
Pts received mosun as monotherapy (n=35), with polatuzumab vedotin (n=27), with CHOP/CHP-based regimen (n=6), with lenalidomide (n=3), or with an experimental agent (n=2)...Most (85%) CRS events were managed conservatively (i.e., acetaminophen, diphenhydramine, and/or IV fluids)...Conclusion In our experience, mosun carried a low risk of CRS (29%) and required little utilization of high-cost treatments like tocilizumab and ICU stays, which is reassuring for use in community practice. Our findings indicate that pts receiving mosun fist line and/or receiving CHOP concurrently have greater odds of CRS with the first admin; these factors should inform admin setting as mosun
- |||||||||| Columvi (glofitamab-gxbm) / Roche, Lunsumio (mosunetuzumab-axgb) / Roche, Epkinly (epcoritamab-bysp) / Genmab, AbbVie
Effect of Consolidation with Allogeneic Hematopoietic Cell Transplant Versus No Consolidation in Patients with Non-Hodgkin Lymphomas Treated with Bispecific Antibodies (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3413;
The two groups (HSCT versus no consolidation) significantly differed in median age at BsAb administration (57 [range 22-71] vs 69 years [range 38-82], p=0.001), primary refractory disease (16 [39.0%] vs 8 [21.6%], p=0.001), prior administration of chimeric antigen T-cell receptor (20 [48.8%] vs 1 [2.7%], p<0.001), number of median lines at which BsAb was administered (4 [range 3-11] vs 3 [range 3-12], p=0.001) and type of administered BsAb (glofitamab 21 [51.2%] vs 17 [45.9%], epcoritamab 7 [17.1%] vs 20 [50.4%], mosunetuzumab 1 [2.4%] vs 0, ondronextamab 11 [26.8%] vs 0, BsAb antiCD22-CD3 1 [2.4%] vs 0, p<0.001)...Thirty-eight (91.7%) pts received reduced intensity conditioning protocols, and 30 (73.2%) received post-transplant cyclophosphamide as graft-versus-host-disease prophylaxis...Conclusions : HSCT consolidation does not seem to be associated with improved survival outcomes, especially for pts reaching a PR or CR during BsAb treatment. These results should be confirmed in a larger study population with a prolonged follow-up.
- |||||||||| Columvi (glofitamab-gxbm) / Roche, Lunsumio (mosunetuzumab-axgb) / Roche, Epkinly (epcoritamab-bysp) / Genmab, AbbVie
Allogeneic Stem Cell Transplantation As Consolidation Therapy in Patients with Relapsed-Refractory B-Cell Lymphoma Exposed to Bispecific Antibodies: A Study on Behalf of Grupo Espa (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3393;
Glofitamab (n=22, [45.8%]) was the most used BsAb, followed by ondronextamab (n=13 [27.1%]), epcoritamab (n=11 [22.9%]), mosunetuzumab (n=1 [2.1%]) and antiCD3-CD22 (n=1 [2.1%])...Reduced intensity conditioning (RIC) regimens were used in 44 (91.7%) pts and the most common GVHD prophylaxis was post-transplant cyclophosphamide-based in 40 (83.3%)...A lower incidence of RI/POD and a higher incidence of aGVHD were observed in those previously exposed to BsAb. These results should be confirmed in a larger cohort of pts with prolonged FU.
- |||||||||| Real-World Management Patterns of Acute Toxicity Following Bispecific Antibody Therapy for Patients with B-Cell Lymphoma - the Geltamo (Spanish Lymphoma Group) Experience (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3152;
Forty-four percent had received previous chimeric antigen receptor T-cell therapy (77% in the aggressive non-Hodgkin lymphoma [aNHL] cohort) and 57% had been exposed to bendamustine (86% for FL)...The patients not hospitalized on a scheduled basis all belonged to CAR-T centers (2 mosunetuzumab, 4 glofitamab, 4 epcoritamab)...Tocilizumab was administered in 20% of patients (1 dose in 90% of cases) and 34% required steroids (median 3 days (IRQ 2-10)); 1 patient was admitted to intensive care with a complete heart block, requiring a pacemaker...Considering the favourable toxicity profile, a lower rate of scheduled hospital admission could be explored. Additional follow-up is necessary to consolidate these safety data and obtain long-term efficacy results.
- |||||||||| Risk Factors for Severe Infection in Patients Receiving Bispecific Antibody Therapies for Lymphoma (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3148;
We evaluated characteristics of infection including time to infection, time from last treatment of bendamustine, autologous SCT, or CAR-T to infection, and outcomes after infection...17 R/R patients received BsAb as combination therapy with Polatuzumab-CHP (n=5), R-DHAOx (n=3), GemOx (n=3), lenalidomide (n=5), or RCHOP (n=1)...Patients were treated with epcoritamab (n=39), glofitamab (n=11), mosunetuzumab (n=16), and plamotamab (n=18)...Our study confirms that patients receiving BsAb have a high risk of severe infections, even in patients treated in the frontline setting or while on prophylaxis. Multivariate analysis showed no difference in risk of severe infection with regards to combination therapy, histology, product, or previous treatment and further research with larger cohorts is warranted to fully understand risk factors for infection in this high risk patient population.
- |||||||||| Risk Factors for Cytokine Release Syndrome in Patients Receiving Bispecific Antibodies for B-Cell Lymphoma: A Single-Center, Retrospective Cohort Study (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3115;
Patients were treated with epcoritamab (Epco) (n=39, 46.4%), glofitamab (Glofit) (n=11, 13.1%), plamotamab (Plamo) (n=18, 21.4%) and mosunetuzumab (Mosun) (n=16, 19.1%)...CRS was managed with additional steroids in 14 patients (29.2%) and tocilizumab in 15 patients (31.3%)...Inflammatory marker levels, prior CAR-T, and prior bendamustine did not impact the risk of CRS. Further studies in larger data sets are needed to identify patients of high CRS risk to allow for early management, and of low risk to allow for treatment in the outpatient setting.
- |||||||||| Patterns of Use and Outcomes of Novel Agents in Patients with Relapsed or Refractory Large B-Cell Lymphoma: A Single-Center Retrospective Analysis (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3098;
This approach reuses recent trial data to establish contemporary benchmarks for the design of new trials before real world evidence can be generated with a change in standard of care. Introduction In addition to chimeric antigen receptor T-cell therapy (CAR-T), 6 novel agents are approved in the United States for relapsed/refractory (r/r) large B-cell lymphoma (LBCL) : polatuzumab (pola) in combination with bendamustine (B) and rituximab (R), tafasitamab plus lenalidomide (tafa/len), loncastuximab (lonca), selinexor, and two CD3xCD20 bispecific antibodies (BsAb) (epcoritamab and glofitamab)...Pola (alone or with R
- |||||||||| Outcomes of Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with R-GemOx: A Multi-Center Retrospective Cohort Study (Halls G-H (San Diego Convention Center)) - Nov 6, 2024 - Abstract #ASH2024ASH_3084;
P=N/A
R-GemOx is used as a comparator arm in several active phase III clinical trials for R/R DLBCL, including the POLARGO (polatuzumab vedotion and R-GemOx), STARGLO (glofitamab and GemOx), SUNMO (mosunetuzumab and polatuzumab vedotin), LOTIS-5 (loncastuximab tesirine and rituximab), and EPCORE DLBCL-1 (epcoritamab) studies...This study demonstrates real-world evidence of the efficacy of R-GemOx in a large cohort of patients with R/R DLBCL from the US over a long period, including both transplant-eligible and -ineligible patients, and patients treated in the CAR T era. These data aid in providing a benchmark for active clinical trials in the rapidly evolving landscape of R/R DLBCL therapies and allow potential comparison to a real-world cohort of patients with a broad range of clinical characteristics.
- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche
Dual HDAC and EZH2 Inhibition Primes Mosunetuzumab for the Treatment of Germinal Center-Derived B-Cell Lymphoma (Marriott Grand Ballroom 11-13 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_1988;
P1
In conclusion, dual BEL+TAZ treatment increases MHC/CD20 expression on malignant B cells and activates peripheral T cells, priming the tumor microenvironment for MOSUN therapy. Taken together, our findings support dual HDAC and EZH2 inhibition as a potential means to prime immunotherapy and improve outcomes in GCB lymphomas.
- |||||||||| Efficacy, Toxicity, and Predictors of Outcomes with CD3-CD20 Bi-Specific Antibodies Post CAR T-Cell Failure for Aggressive B-Cell Lymphoma (Marriott Grand Ballroom 8-9 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_1420;
12 pts (19%) received BsAbs in combination with an adjunctive therapy (6= Revlimid, 2= XRT, 1= Zanubrutinib, 1= BV, 1= Polatuzumab, 1= Azacitidine)...6 pts received tocilizumab and 7 pts received steroids for CRS...After BsAbs failure, mOS was 75 d. Prior bendamustine exposure, use of adjunctive therapy with BsAbs, BsAbs construct, onset of CRS or use of steroids for toxicity management with BsAbs, did not impact PFS and OS with BsAbs treatment...In pts with prior CAR T, elevated LDH, DHL, and early CART failure within 90 days appear to be negative predictors of survival for treatment with BsAbs with dismal outcomes after BsAb failure. These pt subsets should be prioritized for clinical trials evaluating alternative novel therapies.
- |||||||||| Polivy (polatuzumab vedotin-piiq) / Roche, Lunsumio (mosunetuzumab-axgb) / Roche, Gazyva (obinutuzumab) / Roche, Biogen
Enrollment closed, Trial completion date, Trial primary completion date: NCI-2021-12489: Mosunetuzumab With or Without Polatuzumab Vedotin and Obinutuzumab for the Treatment of Untreated Indolent B-Cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - Oct 31, 2024
P2, N=42, Active, not recruiting,
This model-based study suggests that Z+O is a cost-effective treatment option compared to mosun for 3L+ R/R FL in the US. Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025
- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche, Rituxan (rituximab) / Roche
TRIAL IN PROGRESS: CTEP 10590, NORM: NODULAR LYMPHOCYTE-PREDOMINANT HODGKIN LYMPHOMA PATIENTS TREATED IN A RANDOMIZED PHASE II TRIAL WITH EITHER RITUXIMAB OR MOSUNETUZUMAB (Gro) - Oct 31, 2024 - Abstract #ISHL2024ISHL_140;
Exploratory analyses include assessing molecular response by sequencing cell-free DNA, RNAsequencing and whole exome sequencing.We base our sample size justification on a log rank test comparing PFS between the two treatment groups with assumed 2-year PFS rates of 50% (rituximab) versus 75% (mosunetuzunab) with a one-sided type I error rate of 10% and 85% power, accrual period of 3 years and the maximum trial duration of 5 years. The expected sample size is 56 under the null hypothesis and 62 under the alternative hypothesis.The study is open for accrual in the US and Canada since January 2024.
- |||||||||| Ordspono (odronextamab) / Regeneron, Lunsumio (mosunetuzumab-axgb) / Roche, Epkinly (epcoritamab-bysp) / Genmab, AbbVie
Journal: Bispecific antibodies in follicular lymphoma. (Pubmed Central) - Oct 31, 2024
A third agent, odronextamab, remains under review by regulatory agencies...Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.
- |||||||||| MODULE 4: Bispecific Antibody Therapy for FL and Other Lymphoma Subtypes (Manchester Grand Hyatt San Diego, Seaport Ballroom ABCD; In-Person; Virtual) - Oct 5, 2024 - Abstract #ASH2024ASH_136;
CD3 This program is supported by educational grants from Bristol Myers Squibb, Genentech, a member of the Roche Group and Regeneron Pharmaceuticals Inc.Updated efficacy and safety data from the pivotal Phase II GO29781 study evaluating mosunetuzumab monotherapy for patients with R/R FL FDA approval of mosunetuzumab for R/R FL; optimal incorporation considering other available treatment options Efficacy and safety outcomes with epcoritamab in the pivotal EPCORE NHL-1 trial resulting in the recent FDA approval for patients with R/R FL Published research findings with and potential clinical role of odronextamab in the treatment of R/R FL; FDA decision to decline approval of odronextamab for R/R FL because of confirmatory trial enrollment issues Documented antitumor activity of other bispecific antibodies, such as glofitamab, in patients with FL Ongoing and planned evaluations of bispecific antibodies in combination with other systemic therapies for R/R FL Available data with, ongoing investigation of and potential clinical role for bispecific antibodies for other NHL subtypes
- |||||||||| EVOLVE-205 / EvolveImmune Therap
EVOLVE205, a highly potent 2:1 CD20-targeted CD2 co-stimulatory T cell engager engineered for the treatment of B cell malignancies and B cell autoimmune diseases (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1907;
Background T cell engager CD3-bispecifics have improved the treatment of patients with B cell lymphomas leading to recent approvals of the CD20-targeted CD3 bispecifics Glofitamab, Mosunetuzumab, and Epcoritamab for patients with relapsed, refractory diseases...Importantly, the tumor-killing potency of EVOLVE205 was improved by up to 60-fold compared to clinical benchmarks, and by over 1,000-fold compared to B cell depleting therapeutics (BCDTs) such as Rituximab...Conclusions CD2 costimulation integrated EVOLVE205 may provide sustained and potent T cell activation potentially to induce durable anti-tumor response in patients, while demonstrating good developability and favorable IgG-like pharmacokinetics in mice. EVOLVE205 is a highly differentiated CD20-targeted immunotherapy capable of providing deep and durable tissue and peripheral B cell depletion with favorable cytokine release profile compared to clinically available CD20-targeted TCE therapies and BCDTs for the treatment of B cell lymphomas and B cell-mediated autoimmune diseases.
- |||||||||| EVOLVE-205 / EvolveImmune Therap
EVOLVE205, a highly potent 2:1 CD20-targeted CD2 co-stimulatory T cell engager engineered for the treatment of B cell malignancies and B cell autoimmune diseases (Grand Ballroom AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1897;
Background T cell engager CD3-bispecifics have improved the treatment of patients with B cell lymphomas leading to recent approvals of the CD20-targeted CD3 bispecifics Glofitamab, Mosunetuzumab, and Epcoritamab for patients with relapsed, refractory diseases...Importantly, the tumor-killing potency of EVOLVE205 was improved by up to 60-fold compared to clinical benchmarks, and by over 1,000-fold compared to B cell depleting therapeutics (BCDTs) such as Rituximab...Conclusions CD2 costimulation integrated EVOLVE205 may provide sustained and potent T cell activation potentially to induce durable anti-tumor response in patients, while demonstrating good developability and favorable IgG-like pharmacokinetics in mice. EVOLVE205 is a highly differentiated CD20-targeted immunotherapy capable of providing deep and durable tissue and peripheral B cell depletion with favorable cytokine release profile compared to clinically available CD20-targeted TCE therapies and BCDTs for the treatment of B cell lymphomas and B cell-mediated autoimmune diseases.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab-axgb) / Roche, ERY974 / Roche
Organ-specific delivery of a mRNA-encoded bispecific T cell engager targeting Glypican-3 in hepatocellular carcinoma (Grand Ballroom AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1755;
Background Bispecific T-cell engaging antibodies (BiTEs) have been clinically validated (e.g., blinatumomab, mosunetuzumab) but are mostly limited to hematological cancers...MTS105, at dose levels associated with a significantly lower peripheral BiTE Cmax (maximum concentration) and AUC (area under the curve), achieved a better anti-tumor efficacy than the Fc-domain-containing antibody-based BiTE (ERY974)...Conclusion The mRNA-encoded BiTE demonstrated optimal tissue/tumor-specific PK, safety and potent anti-tumor activity in preclinical models. MTS105 is currently in early human trials to assess its safety and preliminary efficacy.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab-axgb) / Roche, ERY974 / Roche
Organ-specific delivery of a mRNA-encoded bispecific T cell engager targeting Glypican-3 in hepatocellular carcinoma (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_804;
Background Bispecific T-cell engaging antibodies (BiTEs) have been clinically validated (e.g., blinatumomab, mosunetuzumab) but are mostly limited to hematological cancers...MTS105, at dose levels associated with a significantly lower peripheral BiTE Cmax (maximum concentration) and AUC (area under the curve), achieved a better anti-tumor efficacy than the Fc-domain-containing antibody-based BiTE (ERY974)...Conclusion The mRNA-encoded BiTE demonstrated optimal tissue/tumor-specific PK, safety and potent anti-tumor activity in preclinical models. MTS105 is currently in early human trials to assess its safety and preliminary efficacy.
- |||||||||| Polivy (polatuzumab vedotin-piiq) / Roche, Lunsumio (mosunetuzumab-axgb) / Roche, Rituxan (rituximab) / Roche
Enrollment closed, Trial completion date, Trial primary completion date: SUNMO: A Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin Compared to Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma (clinicaltrials.gov) - Sep 20, 2024
P3, N=222, Active, not recruiting,
Trial completion date: Jul 2028 --> Mar 2029 | Trial primary completion date: Jul 2026 --> Mar 2027 Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Feb 2027 | Trial primary completion date: May 2025 --> Feb 2025
- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche
Enrollment closed, Monotherapy: MorningSun: A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab Monotherapy in Participants With Select B-Cell Malignancies (clinicaltrials.gov) - Sep 20, 2024
P2, N=345, Active, not recruiting,
Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Feb 2027 | Trial primary completion date: May 2025 --> Feb 2025 Recruiting --> Active, not recruiting
- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche
Enrollment open: CO41942: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokinetics of SC Versus IV Mosunetuzumab + Len in Participants With Follicular Lymphoma (clinicaltrials.gov) - Sep 19, 2024
P1/2, N=187, Recruiting,
Recruiting --> Active, not recruiting Active, not recruiting --> Recruiting
- |||||||||| EVOLVE-205 / EvolveImmune Therap
EVOLVE205, a highly potent 2:1 CD20-targeted CD2 co-stimulatory T cell engager engineered for the treatment of B cell malignancies and B cell autoimmune diseases (George R. Brown Convention Center - Level 3 - Grand Ballroom A) - Sep 18, 2024 - Abstract #SITC2024SITC_184;
Background T cell engager CD3-bispecifics have improved the treatment of patients with B cell lymphomas leading to recent approvals of the CD20-targeted CD3 bispecifics Glofitamab, Mosunetuzumab, and Epcoritamab for patients with relapsed, refractory diseases...Importantly, the tumor-killing potency of EVOLVE205 was improved by up to 60-fold compared to clinical benchmarks, and by over 1,000-fold compared to B cell depleting therapeutics (BCDTs) such as Rituximab...Conclusions CD2 costimulation integrated EVOLVE205 may provide sustained and potent T cell activation potentially to induce durable anti-tumor response in patients, while demonstrating good developability and favorable IgG-like pharmacokinetics in mice. EVOLVE205 is a highly differentiated CD20-targeted immunotherapy capable of providing deep and durable tissue and peripheral B cell depletion with favorable cytokine release profile compared to clinically available CD20-targeted TCE therapies and BCDTs for the treatment of B cell lymphomas and B cell-mediated autoimmune diseases.
- |||||||||| Lunsumio (mosunetuzumab-axgb) / Roche
Review, Journal: Mosunetuzumab for the treatment of follicular lymphoma. (Pubmed Central) - Sep 11, 2024
At the same time, it improves outcomes in the evolving landscape of FL management, even in post-CAR-T FL patients. Prognostic factors and targetable mechanisms of resistance need to be explored.
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