AMG 211 / Amgen - LARVOL DELTA

Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: University of Washington | N=20 ➔ 11 | Trial completion date: Jul 2028 ➔ May 2026 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2027 ➔ May 2026; The trial closed early due to slow accrual.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: University of Washington | N=40 ➔ 20 | Trial completion date: Jul 2027 ➔ Jul 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Washington | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Individual organoid level analyses reveal hidden tumor molecular heterogeneity (AACR 2023) - "In a high tumor mutation burden line (MTB111), 12/17 spikes showed subclonal alterations in APCA896V, F1515C, Q1544* that were not present in the parent culture... PDCOs identified subclonal alterations at the single-organoid level and are an exciting tool to study tumor heterogeneity. The spikes presented less subclonal variants than the parent but were largely not clonal. Future implications of using heterogeneity data from single organoids in therapeutic decisions are warranted."

Clinical • Heterogeneity • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • TMB

Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma. (PubMed, PLoS Comput Biol) - "The biodistribution of TCEs was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. The final model simulations indicated that the number of immune synapses is similar (~55/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in an IgG format and AMG420 in a BiTE format, at their respective efficacious doses in multiple myeloma patients. This result demonstrates the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs, thus suggesting that this framework can be applied to other targets to provide a quantitative means to facilitate model-informed best-in-class TCE discovery and development."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • CEACAM5

Phase 1 Study of AMG 211/MEDI-565 Administered as Continuous Intravenous Infusion (cIV) for Relapsed/Refractory Gastrointestinal (GI) Adenocarcinoma (ESMO 2018) - P1; "PD markers confirmed BiTE® mechanism of action. However, despite an acceptable safety profile immunogenicity leading to insufficient exposure for objective responses precluded the definition of a therapeutic window for AMG 211."

P1 data • Biliary Cancer • Cholangiocarcinoma • Colorectal Cancer • Pancreatic Cancer

A Phase 1 Study of AMG 211 in Participants With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1; N=45; Terminated; Sponsor: Amgen; Completed ➔ Terminated; The study was terminated because of immunogenicity and business decision.

Clinical • Trial termination • Gastrointestinal Cancer • Gastrointestinal Disorder • Neutropenia • Oncology • Solid Tumor

89Zr-labeled Bispecific T-cell Engager AMG 211 PET Shows AMG 211 Accumulation in CD3-rich Tissues and Clear, Heterogeneous Tumor Uptake. (PubMed, Clin Cancer Res) - "This first-in-human study shows high, specific Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter- and intra-individual heterogeneous tumor uptake."

Heterogeneity • Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology

Phase 1 dose escalation study of MEDI-565, a bispecific T-cell engager that targets human carcinoembryonic antigen (CEA), in patients with advanced gastrointestinal (GI) adenocarcinoma (ASCO-GI 2016) - P1, N=39; NCT01284231; Sponsor: MedImmune; "MEDI-565 exposures increased in approximately dose-proportional manner, with clearance (35–77 L/d) and half-life (2–7 h) typical of drug class. ADA had minor impact; 19 pts (48.7%) had ADAs, 5/39 (12.8%) with high titer, with decreased MEDI-565 concentrations in 2 pts. Plasma inflammatory cytokines were elevated posttreatment in several pts at 1.5- and 3-mg (no dex) dose levels....The MTD of MEDI-565 in pts with GI adenocarcinomas was 5 mg with dex. PK was linear, with fast clearance and short half-life. No objective responses were observed."

P1 data • Oncology

A Phase 1 Study of AMG 211 in Subjects With Advanced Gastrointestinal Cancer (clinicaltrials.gov) - P1; N=78; Recruiting; Sponsor: Amgen; Trial primary completion date: Jun 2017 ➔ Sep 2017

Trial primary completion date • Biosimilar • Gastric Cancer • Gastrointestinal Cancer • Oncology

Molecular Imaging of Radiolabeled Bispecific T-cell Engager 89Zr-AMG211 Targeting CEA-positive Tumors. (PubMed, Clin Cancer Res) - P1; "89Zr‑AMG211 showed dose‑dependent CEA‑specific tumor targeting and localization in viable tumor tissue. Our data enabled its use to clinically evaluate AMG 211 in vivo behavior."

Journal

"#MolecularTemplates Announces FDA Acceptance of IND Application for #MT5111, An Engineered Toxin Body Targeting #HER2 $MTEM https://t.co/IYhP99GJ2k" (,@1stOncology)