blinatumomab subcutaneous / Amgen - LARVOL DELTA

Efficacy of single-agent subcutaneous blinatumomab in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL): Results from a phase 1/2 dose expansion study with extended follow-up (ASH 2025) - P1/2 | "At baseline, patients had received a median of 2 prior lines of therapy (range, 1–7),which included cIV blinatumomab in 17 (22%), chimeric antigen receptor T-cells in 14 (18%), HSCT in 23(29%), and inotuzumab ozogamicin in 26 (33%) patients. Consistent with prior findings, single-agent SC blinatumomab maintained durable remissionsand OS in this extended follow-up analysis. These outcomes were observed across the 250/500 and500/1000 doses and were independent of HSCT status. Compared to our previous report, this analysisincludes additional follow-up and updated post-HSCT outcomes."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Septic Shock

Single-Agent Subcutaneous Blinatumomab for Advanced B-Cell Acute Lymphoblastic Leukemia: Long-Term Follow-up from a Phase 1b Dose Expansion Cohort (ASH 2024) - P1/2 | "Of these, 9 pts (33%) were primary refractory, 8 pts (30%) had relapsed after prior HSCT, 4 pts (15%) had relapsed after prior CD19 CAR T–cell therapy, 7 pts (26%) had prior inotuzumab ozogamycin, and 5 pts (19%) had previously received cIV blinatumomab. The trial continues to accrue. These results warrant further evaluation of SC blinatumomab."

Metastases • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL (clinicaltrials.gov) - P1/2 | N=281 | Recruiting | Sponsor: Amgen | Trial primary completion date: Dec 2027 ➔ Jul 2027

Minimal residual disease • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Subcutaneous Blinatumomab for Treatment of Adult Patients With CD19-Positive Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov) - P2 | N=78 | Not yet recruiting | Sponsor: West Virginia University

New P2 trial • Hematological Malignancies • Leukemia • Oncology

Phase 2 Study to Assess the Safety and Efficacy of Subcutaneous Blinatumomab in Patients With Measurable Residual Disease Positive B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Next Questions: Acute Lymphoblastic Leukemia (SOHO 2025) - "The incorporation of the CD3/CD19 bispecific T-cell engager, blinatumomab, and the anti-CD22 monoclonal antibody-drug conjugate, inotuzumab-ozogamicin, for newly diagnosed Ph-negative B-cell ALL have led to promising survival outcomes in the frontline setting for B-cell ALL...In patients at high risk of CNS relapse — such as those with high baseline white blood cell counts (>70 × 10 9) 3— high-dose cytarabine and methotrexate should be incorporated, especially if allogeneic stem cell transplant (allo-SCT) is not pursued in first complete remission (CR1)...Efforts to improve the outcomes in this subgroup include the hyper-CVAD chemotherapy backbone in combination with nelarabine and pegylated asparaginase, which results in a 3-year OS of around 74%. Furthermore, the addition of venetoclax may improve outcomes, at least in a subset of patients with early T-cell precursor (ETP) ALL...14–17 Conclusions The future of ALL treatment includes the continued optimization..."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD5 • CD7 • KMT2A

Phase II Study of the Combination of Subcutaneous Blinatumomab and Olverembatinib in Patients With Philadelphia Chromosome (ph)-Positive and/or BCR::ABL1 Positive Acute Lymphoblastic Leukemia (ALL) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

A Phase 2 Study to Assess the Safety and Efficacy of Subcutaneous Blinatumomab in Combination With Low Intensity Chemotherapy in Older Patients With Newly Diagnosed B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL (clinicaltrials.gov) - P1/2 | N=281 | Recruiting | Sponsor: Amgen | Active, not recruiting ➔ Recruiting

Enrollment open • Minimal residual disease • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study of Subcutaneous Blinatumomab in Children With R/R and and MRD+ B-Cell Precursor Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1/2 | N=104 | Not yet recruiting | Sponsor: Amgen

Minimal residual disease • New P1/2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL (clinicaltrials.gov) - P1/2 | N=281 | Active, not recruiting | Sponsor: Amgen | N=125 ➔ 281

Enrollment change • Minimal residual disease • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy or convenience? Subcutaneous blinatumomab as a promising new treatment for B-cell acute lymphoblastic leukaemia. (PubMed, Lancet Haematol) - No abstract available

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

COMPARATIVE EFFICACY OF THE GIMEMA LAL1913 STANDARD CHEMOTHERAPY PROTOCOL VERSUS THE STANDARD ARM OF THE E1910 TRIAL IN MRD-NEGATIVE PH-NEGATIVE ALL: A MAIC ANALYSIS (EHA 2025) - "In the E1910 trial (Litzow et al, NEJM 2024), Ph- B-ALL patients MRD- after induction treatment were randomized to receive as consolidation standard of care chemotherapy (SOC) or SOC plus blinatumomab. The GIMEMA LAL1913 chemotherapy regimen offers outcomes comparable to those of the E1910 trial's standard arm in MRD- Ph- B-ALL, supporting the clinical equivalence of the Italian standard approach. These findings also provide indirect evidence of the superiority of blinatumomab and to advocate for the adoption of blinatumomab-based consolidation, to further improve outcomes also in MRD- Ph- B-ALL patients."

Clinical • Minimal residual disease • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia

SAFETY AND EFFICACY OF SINGLE-AGENT SUBCUTANEOUS BLINATUMOMAB IN ADULTS WITH RELAPSED/REFRACTORY (R/R) B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL): RESULTS FROM A PHASE 1/2 DOSE EXPANSION STUDY (EHA 2025) - P1/2 | "In this large cohort of 88 pts with R/R B-ALL, single agent SC blinatumomab, resulted in high efficacy, with high MRD-negativity rate and acceptable safety profile. The trial is ongoing and will continue to assess efficacy and AE management in phase 2."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Inflammation • Leukemia • Oncology

Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial. (PubMed, Lancet Haematol) - P1/2 | "Treatment with subcutaneous blinatumomab at the two dose regimens of 250 μg/500 μg and 500 μg/1000 μg resulted in promising preliminary activity and a manageable safety profile in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. The phase 2 part of the trial is ongoing to further evaluate subcutaneous blinatumomab activity and duration of response."

Journal • P1/2 data • Retrospective data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Neutropenia • Oncology

Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial (Lancet Haematol) - P1/2 | N=125 | NCT04521231 | Sponsor: Amgen | "Of the 88 patients included in the analysis at the data cutoff of Nov 28, 2024, 36 (41%) were treated with the 250 μg/500 μg regimen and 52 (59%) with the 500 μg/1000 μg regimen....Serious adverse events occurred in 70 (80%) of 88 patients and included CRS (33 [38%] patients), ICANS (20 [23%] patients), and neurotoxicity (six [7%] patients). No treatment-related deaths were reported. Consistent pharmacokinetics with dose-proportional exposures was observed following subcutaneous administration. Based on the totality of data, including efficacy, safety, and pharmacokinetic data, the subcutaneous blinatumomab dose regimen of 250 μg/500 μg was selected as the recommended phase 2 dose."

P1/2 data • B Acute Lymphoblastic Leukemia

Treatment of Older Patients With ALL. (PubMed, Am Soc Clin Oncol Educ Book) - "In Ph-negative ALL, the duration and intensity of chemotherapy was reduced, and outcomes improved with the addition of inotuzumab ozogamicin (InO) and blinatumomab into the frontline setting...The combination of blinatumomab and ponatinib induced high rates of complete molecular responses and excellent survival, without reliance on HSCT. A subset of patients with elevated WBC count at diagnosis are at particular risk of CNS and systemic relapse and may require additional strategies such as incorporating one to two cycles of high-dose methotrexate/cytarabine into consolidation, and potentially CAR T cells. In T-cell ALL, adding venetoclax into the frontline setting has improved outcomes. In early T-cell precursor ALL, HSCT is still needed. To further improve outcomes in older patients, novel agents such as subcutaneous blinatumomab, CAR T cells, newer-generation TKIs, and menin inhibitors should be investigated in the frontline setting."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • ABL1

Inferior Outcomes in Acute Lymphoblastic Leukemia With Translocation (14;18). (PubMed, Clin Lymphoma Myeloma Leuk) - "The outcome of B-ALL with t(14;18)(q32;q21) is poor. Incorporating immune-therapies, chimeric antigen receptor (CAR)-T cell therapy, with or without HSCT, into the treatment regimens, might further improve outcomes."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation • BCL2

Fourth Quarter Product and Pipeline Update…BLINCYTO (PRNewswire) - "A Phase 1/2 study of subcutaneous blinatumomab is ongoing in the dose-expansion and optimization phase in adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025."

Trial status • B Acute Lymphoblastic Leukemia

A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients (clinicaltrials.gov) - P1/2 | N=125 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Frontline immunotherapeutic combination strategies in adult B-cell acute lymphoblastic leukemia: reducing chemotherapy intensity and toxicity and harnessing efficacy. (PubMed, Leuk Lymphoma) - "Using immunotherapeutic agents like inotuzumab ozogamicin (InO), blinatumomab, or chimeric antigen receptor T (CAR T)-cell therapy in frontline adult B-cell acute lymphoblastic leukemia (B-ALL) therapy is promising...Modifications of dosing and administration schedules, as with the fractionated InO schedule with low-intensity chemotherapy, and subcutaneous blinatumomab, appear to reduce the toxicity and improve the anti-ALL efficacy. CAR T-cell therapies like brexucabtagene autoleucel as a consolidation approach have shown positive outcomes...Newer generation CAR T-cell products like obecabtagene autoleucel appear as effective and safer. Better disease monitoring through next generation sequencing based measurable residual disease analysis could identify patients where treatment intensification including HSCT, or deintensification, is suitable."

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

A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Amgen | Trial completion date: Jul 2032 ➔ Mar 2029 | Trial primary completion date: Feb 2031 ➔ Oct 2027

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

AMGEN REPORTS SECOND QUARTER 2024 FINANCIAL RESULTS (PRNewswire) - "A Phase 1/2 study of subcutaneous blinatumomab continues to enroll adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025."

Trial status • B Acute Lymphoblastic Leukemia

A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Amgen | Trial completion date: Dec 2032 ➔ Jul 2032 | Trial primary completion date: Jul 2031 ➔ Feb 2031

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

A Study of Subcutaneous Blinatumomab Administration in Acute Lymphoblastic Leukemia (ALL) Patients (clinicaltrials.gov) - P1/2 | N=125 | Recruiting | Sponsor: Amgen | Trial completion date: Sep 2028 ➔ Dec 2032 | Trial primary completion date: Nov 2026 ➔ Jul 2031

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