XmAb968 / Xencor - LARVOL DELTA

Differential CD38 Glycosylation Patterns in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia: Implications for Targeted Immunotherapy (ASH 2024) - "Targeted therapies against CD38, including monoclonal and bispecific antibodies such as XmAb18968 (Xencor), have demonstrated efficacy with manageable toxicity...After PNGase F treatment, CD38 recognition varied : it was enhanced in THP-1 but reduced in HL-60 cell lines, indicating that glycosylation differentially affects antibody recognition across leukemia types. Conclusion : This study highlights significant heterogeneity in CD38 expression and glycosylation across leukemia types and stages, impacting the binding and efficacy of CD38-targeted antibodies."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

PRO00041908: XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Ehab L Atallah | Recruiting ➔ Active, not recruiting | N=60 ➔ 22 | Trial completion date: Oct 2026 ➔ Apr 2025 | Trial primary completion date: Oct 2025 ➔ Apr 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD38

A Phase 1 Study of CD38-Bispecific Antibody (XmAb18968) for Patients with CD38 Expressing Relapsed/Refractory Acute Myeloid Leukemia (ASH 2023) - P1 | "Twelve of 13 patients (92%) were previously treated with venetoclax based regimen and 31% had prior allogeneic HCT. XmAb18968 is safe and well tolerated in patients with RR-AML. Dose escalation yielded MRD negative CR in RR-AML patients who were MRD positive at study entry. Details on correlative studies examining mechanisms of therapeutic efficacy and resistance will be reported in the main meeting."

Clinical • IO biomarker • P1 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Anemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology • Thrombocytopenia • Transplantation • ASXL1 • CD38 • RUNX1 • TP53

A Phase 1 Study of CD38-Bispecific Antibody (XmAb18968) for Patients with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - P1 | "Major exclusion criteria are hematopoietic cell transplantation within 6 months of enrollment, prior therapy with daratumumab in the last 6 months and active acute graft-versus-host disease. XmAb18968, a novel CD-38 bispecific antibody appears safe and is showing response at the starting dose level in T-ALL. The study is currently enrolling additional patients with T-ALL. Updated analysis with additional patients and details on correlative studies examining mechanisms of therapeutic efficacy will be reported at the main meeting."

Clinical • IO biomarker • P1 data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • Transplantation • CD7

A Phase 1 Study of XmAb18968, a CD3-CD38 Bispecific Antibody for the Treatment of Patients with Relapsed/Refractory Acute Leukemia and T Cell Lymphoblastic Lymphoma (ASH 2021) - "RP2D will be defined as the highest dose level at which none of the first 3 treated subjects, or no more than 1 of the first 6 treated subjects experience a DLT. A minimum of 24 and a maximum of 60 patients will be needed for the dose escalation phase."

Clinical • IO biomarker • P1 data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • Transplantation

A phase 1 study of CD38-bispecific antibody (XmAb18968) for patients with CD38 expressing relapsed/refractory acute myeloid leukemia and T-cell acute lymphoblastic leukemia. (ASCO 2022) - P1 | "A minimum of 24 and a maximum of 60 patients will be enrolled. The study is being conducted at 6 sites in United States and is currently open for enrollment."

Clinical • IO biomarker • P1 data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • Transplantation

XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Ehab L Atallah | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CD38

Xencor Reports First Quarter 2021 Financial Results (Businesswire) - "XmAb717 (PD-1 x CTLA-4): The Company plans to initiate a Phase 2 study in patients with certain molecular subtypes of castration-resistant prostate cancer (CRPC) in mid-2021; Tidutamab (SSTR2 x CD3): The Company plans to initiate a clinical study in patients with Merkel cell carcinoma and small cell lung cancer...in mid-2021; Plamotamab (CD20 x CD3)...The Company plans to initiate the first of these studies, in patients with r/r DLBCL, an aggressive type of non-Hodgkin lymphoma (NHL), in late 2021 or early 2022; XmAb698 (CD38 x CD3): The Company plans to support investigator-initiated studies of XmAb698 (formerly AMG 424), and a new study is currently being planned to start later in 2021...Xencor earned $12.5 million for the development milestone and recognized royalty revenue of $1.4 million on net sales of Monjuvi® during the first quarter of 2021."

New P2 trial • New trial • Sales • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Merkel Cell Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer

Targeting Multiple Myeloma with AMG 424, a Novel Anti-CD38/CD3 Bispecific T Cell-Recruiting Antibody Optimized for Cytotoxicity and Cytokine Release. (PubMed, Clin Cancer Res) - "These findings support the clinical development of AMG 424, an affinity-optimized T cell-recruiting antibody with the potential to elicit significant clinical activity in MM patients."

IO Biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Study Evaluating AMG 424 in Subjects With Multiple Myeloma (clinicaltrials.gov) - P1; N=27; Terminated; Sponsor: Amgen; N=120 ➔ 27; Trial completion date: Mar 2023 ➔ Jun 2020; Recruiting ➔ Terminated; Trial primary completion date: Mar 2023 ➔ Jun 2020; Sponsor business decision not to proceed with the AMG 424 asset.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

Amgen tosses back unwanted bispecific to Xencor as KRAS data on track for 2020 readout (FierceBiotech) - "Amgen has culled a bispecific drug it picked up in a $1.7 billion biobucks deal with Xencor. In its second-quarter results, the biopharma said: 'Phase 1 development of AMG 424, a CD38-CD3 XmAb antibody has been stopped, with rights reverting to Xencor'...Meanwhile, one of the most keenly watched cancer drugs in development, KRAS drug AMG 510 (now known as sotorasib) is still on track to deliver data from a potentially pivotal phase 2 monotherapy study in patients with advanced non-small cell lung cancer (NSCLC) in the coming months, despite ongoing pandemic disruptions to trials."

Licensing / partnership • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Study Evaluating AMG 424 in Subjects With Multiple Myeloma (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: Amgen; Active, not recruiting ➔ Recruiting; N=20 ➔ 120

Clinical • Enrollment change • Enrollment open

"What? Why? What will happen to AMG424 and AMG701 then?" (@Myeloma_Patient)

Study Evaluating AMG 424 in Subjects With Multiple Myeloma (clinicaltrials.gov) - P1; N=20; Active, not recruiting; Sponsor: Amgen; Recruiting ➔ Active, not recruiting; N=120 ➔ 20; Trial completion date: Jul 2021 ➔ Dec 2022; Trial primary completion date: Jul 2021 ➔ Dec 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date