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Real-World Teclistamab Data Shows Comparable Efficacy to Clinical Trials Despite Higher Toxicity Rates in Multiple Myeloma

CAR-TReal World Evidence
  • A multicenter real-world study of 110 patients treated with teclistamab demonstrated a 62% overall response rate and 51% very good partial response rate, comparable to the pivotal MajesTEC-1 trial despite treating a more heavily pretreated population.
  • The incidence of severe cytokine release syndrome and neurotoxicity was substantially higher in real-world practice (3.6% and 4.5% respectively) compared to clinical trials (0.6% each), likely due to higher disease burden in routine practice.
  • Primary intravenous immunoglobulin prophylaxis significantly reduced infection rates by approximately 70%, with patients receiving IVIG showing lower cumulative incidence of grade 3 or higher infections compared to those without prophylaxis.
  • Analysis of FDA adverse event data across BCMA-targeted therapies revealed teclistamab had the highest rates of life-threatening events and death, with infections being the predominant cause of non-relapse mortality.

Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma

NCT03145181Active, Not RecruitingPhase 1
Janssen Research & Development, LLC
Posted 5/16/2017

A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04557098Active, Not RecruitingPhase 2
Janssen Research & Development, LLC
Posted 9/17/2020

India's Indigenous CAR T-Cell Therapy Revolutionizes Cancer Treatment at One-Tenth Global Cost

CAR-TOncologyDrug Approval
  • India has successfully developed NexCAR19, its first indigenous CAR T-cell therapy for blood cancers, priced at approximately Rs 40 lakh ($50,000) compared to $400,000 in the United States.
  • Clinical trials involving 64 patients with advanced lymphoma or leukemia showed promising results, with 67% experiencing significant cancer reduction and about half achieving complete remission.
  • Unlike U.S. approved therapies that use mouse-derived antibody fragments, India's "humanized" CAR T-cells caused fewer severe side effects, with no reported neurologic complications and only 5% experiencing severe cytokine release syndrome.

CAR T-Cell Therapy Shows Promise in Reversing Age-Related Metabolic Dysfunction

CAR-T
  • Researchers have successfully reprogrammed CAR T cells to target and eliminate senescent cells that accumulate with age, demonstrating potential to reverse age-related metabolic decline.
  • The novel senolytic therapy targets urokinase plasminogen activator receptor (uPAR)-positive cells, requiring only a single administration compared to traditional small-molecule approaches that need repeated dosing.
  • In aged mice, the CAR T-cell treatment improved glucose homeostasis and metabolic fitness without observable toxicity, suggesting promising therapeutic applications for age-related conditions.

Bispecific Antibodies: Promising Advances Amid Adoption Challenges in Cancer Treatment

Drug ApprovalOncologyCAR-TMonoclonal Antibody
  • Bispecific antibodies represent a significant advancement in cancer immunotherapy, targeting both tumor antigens and immune cells to enhance cytotoxicity without requiring patient-derived cells like CAR-T therapy.
  • Despite clinical promise with nine FDA-approved bispecific antibodies, adoption faces challenges including transition between inpatient/outpatient settings, insurance coverage, adverse event management, and financial barriers in community settings.
  • Recent approvals of Mosunetuzumab, Glofitamab, and Epcoritamab have shown impressive response rates in relapsed/refractory indolent B-cell lymphomas, with manageable toxicity profiles when using step-up dosing strategies.

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

NCT04663347Active, Not RecruitingPhase 1
Genmab
Posted 11/3/2020

Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma

NCT05994235RecruitingPhase 2
Weill Medical College of Cornell University
Posted 11/1/2023

Glofit and Obin in Follicular Lymphoma and Marginal Zone Lymphoma

NCT05783596RecruitingPhase 2
Reid Merryman, MD
Posted 7/18/2023

Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma

NCT05409066Active, Not RecruitingPhase 3
Genmab
Posted 9/20/2022

CAR-T Followed by Bispecific Antibodies

NCT04889716RecruitingPhase 2
Abramson Cancer Center at Penn Medicine
Posted 11/5/2021

Mosunetuzumab-Lenalidomide Versus Investigator Choices in Patients With Relapsed or Refractory Marginal Zone Lymphoma

NCT06006117RecruitingPhase 3
The Lymphoma Academic Research Organisation
Posted 9/5/2023

A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomide With a US Extension of Mosunetuzumab in Combination With Lenalidomide in Participants With Follicular Lymphoma

NCT04712097Active, Not RecruitingPhase 3
Hoffmann-La Roche
Posted 10/27/2021

Signatures of Response and Resistance to Mosunetuzomab in Follicular Lymphomas (FL)

NCT05529524Completed
The Lymphoma Academic Research Organisation
Posted 11/7/2022

Mosunetuzumab With or Without Polatuzumab Vedotin and Obinutuzumab for the Treatment of Untreated Indolent B-Cell Non-Hodgkin Lymphoma

NCT05169658CompletedPhase 2
University of Washington
Posted 3/23/2022

CRISPR/Cas9 Technology Revolutionizes CAR-T Cell Therapy: Enhancing Efficacy and Overcoming Treatment Barriers

CAR-TGene EditingDrug Approval
  • CRISPR/Cas9 gene editing technology is being integrated with CAR-T cell therapy to address key limitations including immune checkpoint inhibition, T cell exhaustion, and manufacturing challenges.
  • The technology enables precise knockout of immune checkpoint genes like PD-1 and CTLA-4, significantly enhancing CAR-T cell persistence and anti-tumor activity in preclinical studies.
  • CRISPR/Cas9 facilitates development of universal "off-the-shelf" CAR-T cells by eliminating TCR and HLA genes, potentially reducing manufacturing costs and treatment timelines from weeks to days.
  • Despite promising clinical trial results showing safety and feasibility, researchers continue addressing potential safety concerns including off-target effects and chromosomal instability.

Novel Targets and Strategic Sequencing: The Evolving Landscape of T-Cell Redirection Therapies in Multiple Myeloma

OncologyCAR-T
  • CAR T-cell therapies and bispecific antibodies targeting BCMA and GPRC5D are transforming multiple myeloma treatment, with ciltacabtagene autoleucel showing unprecedented efficacy with a median PFS of 34.9 months in heavily pretreated patients.
  • Disease progression rate is a critical factor in therapy selection, with rapidly progressing patients better suited for "off-the-shelf" bispecific antibodies, while patients with indolent disease may benefit more from CAR T-cell therapies despite longer manufacturing times.
  • Strategic sequencing of therapies is crucial, as prior BCMA-directed bispecific antibody treatment significantly reduces the efficacy of subsequent BCMA-targeted CAR T-cell therapy, highlighting the importance of preserving T-cell fitness and considering antigen loss.

A Study of CAR-T Cells Targeting Both BCMA and GPRC5D in Treatment of Relapsed or Refractory Multiple Myeloma

NCT05325801Not Yet RecruitingPhase 1
Zhejiang University
Posted 4/1/2022

A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma

NCT04181827Active, Not RecruitingPhase 3
Janssen Research & Development, LLC
Posted 6/12/2020

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)

NCT04093596Active, Not RecruitingPhase 1
Allogene Therapeutics
Posted 9/23/2019

A Study of MCARH109 and MCARH125 in People With Multiple Myeloma

NCT05431608Active, Not RecruitingPhase 1
Memorial Sloan Kettering Cancer Center
Posted 6/20/2022

A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy

NCT04923893Active, Not RecruitingPhase 3
Janssen Research & Development, LLC
Posted 8/19/2021

MagnetisMM-3: Study Of Elranatamab (PF-06863135) Monotherapy in Participants With Multiple Myeloma Who Are Refractory to at Least One PI, One IMiD and One Anti-CD38 mAb

NCT04649359Active, Not RecruitingPhase 2
Pfizer
Posted 2/2/2021

A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04557098Active, Not RecruitingPhase 2
Janssen Research & Development, LLC
Posted 9/17/2020

Safety and Efficacy of Anti-BCMA/GPRC5D CAR-T Cell Therapy in Treating Relapsed and Refractory Multiple Myeloma(rr/MM)

NCT05509530RecruitingPhase 2
Xuzhou Medical University
Posted 5/1/2022

A Study of CAR-T Cells Targeting GPRC5D in the Treatment of r/r Multiple Myeloma

NCT05016778Active, Not RecruitingEarly Phase 1
Zhejiang University
Posted 6/8/2021

Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma

NCT03361748CompletedPhase 2
Celgene
Posted 12/13/2017

A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

NCT03548207CompletedPhase 1
Janssen Research & Development, LLC
Posted 6/29/2018

Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

NCT03651128Active, Not RecruitingPhase 3
Celgene
Posted 4/16/2019

A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04586426Active, Not RecruitingPhase 1
Janssen Research & Development, LLC
Posted 12/15/2020

A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma

NCT04133636RecruitingPhase 2
Janssen Research & Development, LLC
Posted 11/7/2019

Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT03399799Active, Not RecruitingPhase 1
Janssen Research & Development, LLC
Posted 12/16/2017

A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma

NCT05257083RecruitingPhase 3
Stichting European Myeloma Network
Posted 10/10/2023

A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

NCT04634552RecruitingPhase 2
Janssen Research & Development, LLC
Posted 2/1/2021

MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma

NCT04555551Active, Not RecruitingPhase 1
Memorial Sloan Kettering Cancer Center
Posted 9/8/2020

Bispecific T-Cell Engagers Show Promise as Later-Line Therapies for Relapsed/Refractory DLBCL

CAR-TDrug ApprovalOncology
  • Two bispecific T-cell engagers, epcoritamab-bysp and glofitamab-gxbm, received FDA accelerated approval in 2023 for relapsed/refractory diffuse large B-cell lymphoma, offering new treatment options for heavily pretreated patients.
  • Both agents demonstrate remarkable activity with overall response rates above 50-60% and complete response rates around 40% in patients with CAR T-cell therapy failure, addressing a significant unmet medical need.
  • Epcoritamab offers convenient subcutaneous administration in outpatient settings with manageable cytokine release syndrome rates below 3%, while glofitamab provides fixed-duration therapy with durable responses lasting over one year after treatment completion.
  • These bispecific antibodies may challenge the paradigm that CAR T-cell therapy is the only curative option for relapsed/refractory patients, with emerging data suggesting potential for long-term disease control.

A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-cell Non-hodgkin's Lymphoma

NCT03075696RecruitingPhase 1
Hoffmann-La Roche
Posted 2/21/2017

First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma

NCT03625037Active, Not RecruitingPhase 1
Genmab
Posted 6/26/2018

Anbalcabtagene Autoleucel Shows 84% Response Rate in Relapsed/Refractory Large B-Cell Lymphoma

CAR-T
  • Anbalcabtagene autoleucel (anbal-cel), a novel anti-CD19 CAR T-cell therapy, achieved an 84% objective response rate with 71% complete responses in patients with relapsed/refractory large B-cell lymphoma.
  • The therapy demonstrated durable responses with 68% of patients maintaining complete response at 1 month and 60% at 6 months, showing sustained efficacy over time.
  • Safety profile was manageable with 63.4% of patients experiencing cytokine release syndrome and 19.5% developing neurologic events, consistent with expected CAR T-cell toxicities.
  • The treatment is based on the OVIS platform that downregulates PD-1 and TIGIT expression to enhance CAR T-cell cytotoxicity in the tumor microenvironment.

An Open-Label, Multi-Centre, Phase Ib/II Study Evaluating the Safety and Efficacy of AUTO1, a CAR T Cell Treatment Targeting CD19, in Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia.

2024-512903-38-00Active, Not RecruitingPhase 1/2
Autolus Limited

Study of Efficacy and Safety of CRC01 in Adult Large B-cell Lymphoma Patients

NCT04836507RecruitingPhase 1
Curocell Inc.
Posted 3/2/2021

Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19

NCT02935257RecruitingPhase 1
University College, London
Posted 9/29/2017

Novel BCMA-Targeted Therapies and Emerging Agents Transform Treatment Landscape for Relapsed/Refractory Multiple Myeloma

CAR-TDrug Approval
  • BCMA-directed therapies including CAR T-cell products ide-cel and cilta-cel, along with bispecific T-cell engager teclistamab, have demonstrated unprecedented efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma.
  • Emerging bispecific antibodies elranatamab and talquetamab show promising response rates of 61-74% in triple-class refractory patients, offering new treatment options for those who have exhausted conventional therapies.
  • Novel agents including mezigdomide (a CELMoD), purinostat mesylate (HDAC inhibitor), and bispecific CS1-BCMA CAR T cells are expanding therapeutic options with manageable safety profiles.
  • The treatment paradigm is shifting toward earlier use of BCMA-targeted therapies and novel combinations, as patients increasingly become refractory to multiple drug classes including immunomodulators, proteasome inhibitors, and anti-CD38 antibodies.

Isatuximab, Pomalidomide, Elotuzumab and Dexamethasone in Relapsed And/or Refractory Multiple Myeloma

NCT04835129RecruitingPhase 2
Medical College of Wisconsin
Posted 1/10/2022

Selinexor and Backbone Treatments of Multiple Myeloma Patients

NCT02343042Active, Not RecruitingPhase 1
Karyopharm Therapeutics Inc
Posted 10/1/2015

CAR-T Cell Therapy Shows Promise Despite Significant Safety Challenges in Clinical Trials

CAR-T
  • CAR-T cell therapy demonstrates remarkable efficacy in treating hematological malignancies, with CD19-targeted therapies achieving 67% complete remission rates in acute lymphoblastic leukemia and 82% objective response rates in non-Hodgkin lymphoma patients.
  • Serious adverse events occur in significant proportions of patients, with cytokine release syndrome affecting 11.67% of hematological cancer patients and neurological complications occurring in 20.20% of cases.
  • Management strategies including tocilizumab and corticosteroids have proven effective in controlling severe complications, with most adverse events being reversible when properly managed.
  • Academic centers play a crucial role in CAR-T development, sponsoring 35.4% of clinical trials globally, though Europe lags behind the US and China in trial numbers and industry collaboration.

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