Blincyto (blinatumomab) / Astellas, Amgen, BeiGene - LARVOL DELTA

Recent Development in Bispecific Antibody Immunotherapy for Hematological Malignancies. (PubMed, Crit Rev Oncol Hematol) - "Leading BsAbs, including mosunetuzumab, glofitamab, and blinatumomab, have demonstrated promising efficacy in clinical trials for leukemia and lymphoma subtypes. Despite remaining challenges, particularly in acute myeloid leukemia (AML), ongoing research into new targets and combination therapies is expected to enhance the efficacy of BsAbs in relapsed or refractory (R/R) disease. This review explores the structural and functional innovations of BsAbs, the challenges in current therapies, and their transformative potential in hematological malignancy immunotherapy."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology

IndEx-2: An in vitro model to evaluate the impact of target antigen density on antibody and immune therapeutics (AACR 2025) - "In the first, we have compared CLN978, a novel CD19- TCE developed for B-cell malignancies and autoimmune diseases, with Blinatumomab and demonstrated that the former retained its activity in terms of cytotoxicity and cytokine production at much lower levels of CD19 expression and estimate the threshold for each molecule in a cohort of 10 healthy donors. The tandem CAR exhibited enhanced cytotoxicity when either or both antigens were expressed, whereas the dual CAR required co-expression of both antigens for optimal T-cell activation. These results underscore IndEx-2's robustcapability to evaluate the influence of antigen density on therapeutic safety andefficacy, providing a powerful tool for the development of antibody-based and immune-targeting cancer therapies."

IO biomarker • Preclinical • Hematological Malignancies • Oncology • CD19 • CD22 • HER-2 • IFNG

Feedback-responsive cell factories for dynamic modulation of the unfolded protein response. (PubMed, Nat Commun) - "The sense-and-respond systems that mediate dynamic UPR modulation enhance the production of the therapeutic enzyme tissue plasminogen activator and the bispecific antibody blinatumomab. Our feedback-responsive cell factories provide an innovative strategy for dynamically adjusting the innate cellular stress response and enhancing therapeutic protein manufacturing."

Journal

Two-component T-cell immunotherapy enables antigen pre-targeting to reduce cytokine release without forfeiting efficacy. (PubMed, Nanomedicine) - "αCD19 and αCD20 MATCH, administered in two steps, are both compared to the clinical standard bispecific antibody, blinatumomab...Ultimately, this split-antibody paradigm may enhance antigen targeting while reducing cytokine release, with such safety and efficacy advantages augmented by the future possibility of multi-antigen targeting with MATCH. KEY POINT: Two-component T-cell engager allows for versatility in targeting and tunability in T-cell activation."

Journal • Hematological Malignancies • Lymphoma • Oncology • CD20

Blincyto: “BLINCYTO sales increased 52% YoY in Q1, primarily driven by volume growth.” (Amgen) - Q1 2025 Results

Commercial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Cytokine release syndrome among acute lymphocytic leukemia adults undergoing treatment with blinatumomab in the United States. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Cytokine release syndrome • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy and safety of combination therapy of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and meta-analysis. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Combination therapy • Retrospective data • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

A phase I study of asciminib in combination with dasatinib, prednisone, and blinatumomab for Ph-positive acute leukemia in adults. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03595917 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • P1 data • Hematological Malignancies • Leukemia • Oncology

Epigenetic and phenotypic signatures of T-cell response to blinatumomab in pediatric relapsed and refractory B-ALL. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Pediatrics

Barriers to Blinatumomab Administration and Access: How to Overcome Them (ASCO 2025) - No abstract available

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Who Would and Would Not Benefit From Receiving Blinatumomab in Frontline Treatment of B-Cell Acute Lymphoblastic Leukemia (ASCO 2025) - No abstract available

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Navigating B-Acute Lymphoblastic Leukemia in the Era of Blinatumomab (ASCO 2025) - "In the last year, pivotal new trial results from the Children's Oncology Group have upended the standard of care treatment of patients with B-ALL. Faculty will discuss how treatment paradigms have changed for different subpopulations of patients with B-ALL; the barriers patients and institutions face in delivering blinatumomab, and the future of treatment for B-ALL"

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

AMGEN REPORTS FIRST QUARTER 2025 FINANCIAL RESULTS (PRNewswire) - "Product Sales Performance:... (i) BLINCYTO (blinatumomab) sales increased 52% year-over-year to $370 million in the first quarter, primarily driven by volume growth; (ii) Vectibix (panitumumab) sales increased 8% year-over-year to $267 million in the first quarter, driven by volume growth; (iii) KYPROLIS (carfilzomib) sales decreased 14% year-over-year to $324 million in the first quarter, driven by lower volumes due to increased competition."

Sales • Acute Lymphocytic Leukemia • Colorectal Cancer • Multiple Myeloma

Management of Adult Acute Lymphoblastic Leukemia: A Review. (PubMed, JAMA Oncol) - "The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • CD20 • CD22

Role of External Control Arm (ECA) Derived from Real World Data (RWD) in US FDA Regulatory Approval from 2020-2024 (ISPOR 2025) - "OBJECTIVES: To analyze role of ECA in US FDA approvals ( 2020 - 2024) & summarize the key disease areas leveraging ECA. systematic literature review and analysis of all novel drug approvals including NDA (New Drug Application) and BLA (Biological License Application)submitted from 2020-2024 were analyzed. The percentage of approvals involving external control arms increased steadily, particularly in rare diseases, oncology, and conditions with small or hard-to-recruit patient populations from 2020-2024 2020: Early Exploration (5-7% of Approvals) : 1.Ibrance (palbociclib): Used retrospective RWD to support male breast cancer indication...Blincyto (blinatumomab): Supplemental approvals for rare cancers based on external data. 2021: Accelerated Adoption Amid COVID-19 (10-15% of Approvals) 1.Veklury (remdesivir): Approval supported by real-world hospital data as external comparisons...Keytruda (pembrolizumab): Label expansion for certain cancers using external control..."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

Assessment of Conditional Listing for Highly Uncertain and High-Priced Drugs in Taiwan (ISPOR 2025) - "The review and assessment process were conducted independently by two researchers. A total of 12 drugs were considered for conditional listing between 2022 and 2024, which included Pemazyre, Tepmetko, Qarziba, Kymriah, Vitrakvi, Blincyto, Vydamax, Takhzyro, Polivy, Velexbru, Spevigo, and Koselugo. The conditional listing opens up new opportunities for high-priced drugs. However, the 2-year real-world evidence for Pemazyre remains insufficient for the government to make a final reimbursement decision. Consequently, the results of the HTA will pose challenges in the future in Taiwan."

Pre-transplant blinatumomab and/or inotuzumab ozogamicin therapy for relapsed/refractory acute lymphoblastic and B/myeloid mixed phenotype acute leukemia in adults. (PubMed, Leuk Res) - "In patients in CR at HCT, there was no difference in HCT outcomes at 2 years (OS, 82.4 % vs. 58.8 %; p = 0.324; DFS, 64.2 % vs. 47.1 %; p = 0.496; CIR, 24.1 % vs. 41.2 %; p = 0.375; NRM, 11.8 % vs. 11.8 %; p = 0.950). BLI and/or INO therapy for RR-ALL was associated with better survival after HCT, probably due to the higher CR rate."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Tyrosine kinase inhibitors with blinatumomab versus chemotherapy in Philadelphia-positive acute B-lymphoblastic leukemia. (PubMed, Int J Cancer) - "Severe treatment-related adverse events were significantly less frequent in the TKI and blinatumomab cohort, with no difference in early molecular complete response rates. Our findings, consistent with published prospective trials, highlight the safety and efficacy of TKI and blinatumomab in managing Ph + B-ALL."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Truncated form of human CD19 antigen as a suicide gene to control T-cell alloreactivity: ΔCD19. (PubMed, Haematologica) - "We demonstrated that the exposure of ΔCD19-T-cells to an anti-hCD19-hCD3 T-cell bispecific T-cell engager (BiTE) molecule (structurally identical to blinatumomab, an agent largely used in the treatment of B-cell acute lymphoblastic leukemia) resulted into a prompt elimination of hCD19+/CD3+ cells both in vitro and in an in vivo animal model of mice developing a xenograft reaction mimicking GvHD after infusion of in vitro-activated/expanded human T cells. Importantly, the administration of the anti-hCD19-hCD3 BiTE molecule in the animal model, from one hand led to the improvement of signs and symptoms of GvHD, as well as of the overall-survival of the mice, and from the other, after a drug washout, was associated with the resurge of ΔCD19-T-cells without reoccurrence of GvHD. Our study provides evidence that the ΔCD19 suicide gene used in combination with an anti-hCD19-hCD3 T-cell BiTE molecule could represent a valid and effective strategy to control GvHD occurring after..."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation

Design of the First Clinical Trial of AAV Gene Therapy in Immuno-Oncology (SENTRY-ALL): A Single Dose CD3/CD19 Bi-Specific T-Cell Engager for the Treatment of CD19+ B-Cell Acute Lymphoblastic Leukemia (ASGCT 2025) - P1/2 | "VNX-101 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-CD19/anti-CD3 scFv diabody (termed GP101)...Prior blinatumomab and/or CD19 CAR T-cell treatment is allowed...This trial aims to provide the first clinical experience in the use of AAV gene therapy as a new paradigm for cancer immunotherapy. Disease Focus of Abstract:Cancer Hematologic"

Clinical • Gene therapy • Immuno-oncology • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Fibroblast Activation Protein (FAP) Directed Bispecific Antibodies Target Pediatric Sarcomas (ASGCT 2025) - "We developed a bispecific antibody construct that combined the anti-FAP scFv from clone BIBH 1 (sibrotuzumab) with that of the anti-CD3 scFV LK2-07 (blinatumomab)...Coupled with our lab's novel rAAV expression system, this approach shows promise as a targeted therapy against CAFs and FAP-expressing sarcomas, though further in vivo studies are needed to assess its anti-tumor efficacy. Disease Focus of Abstract:Cancer Solid Tumors"

Clinical • IO biomarker • Fibrosarcoma • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor • CAFs • FAP

Development of an Adeno-Associated Virus Expressing a Secreted T Cell Engager for Long-Term B Cell Ablation with High Transgene Expression to Minimize Vector Dose (ASGCT 2025) - "Serum levels of GP101 were consistently above the lower threshold of the human therapeutic target range (300 pg/mL, based on clinical experience with blinatumomab) at doses of 3.0E10 vg/kg (females) and 1.0E10 vg/kg (males). Based on the mechanism of action, VNX-101 may also be applicable to B cell lymphoma, chronic lymphocytic leukemia, and autoimmune diseases. Disease Focus of Abstract:Cancer Hematologic"

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Repurposing oncology drugs to treat autoimmune disease (ASGCT 2025) - "Rituximab is the first monoclonal antibody approved for treating lymphoma, becoming one of the most popular and versatile drugs in clinical application and revenue...In 2014, Blincyto was approved by the FDA for treating acute lymphoma, opening the door to developing T cell engagers (TCE)...TLR 7/8 agonist Resiquimod was applied on the ear of immunodeficient mice after 14 weeks of HSC reconstitution, 3 times a week, with a modeling period of 6 weeks... Developing new drugs requires a significant investment of time and economic costs. The research on drug repurposing has significant advantages over developing new drugs. Humanized SLE models exhibit similar pathological features seen in SLE patients such as high levels of auto-antibodies and pathogenic B cells."

Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Oncology