AMG 119 / Amgen - LARVOL DELTA

Delta-like ligand 3 in small cell lung cancer: potential mechanism and treatment progress. (PubMed, Crit Rev Oncol Hematol) - "The Phase III clinical trials of Rova-T, a drug targeting DLL3, have not yielded the expected results. However, other drugs that target DLL3, such as AMG119, AMG757 and DLL3-targeted NIR-PIT, bring new ideas for SCLC treatment. Overall, DLL3 remains a valuable target for SCLC."

Journal • Review • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1 | N=6 | Suspended | Sponsor: Amgen | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting Delta-like ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC). (PubMed, J Clin Pharmacol) - "AMG 119 has been clinically safe and well tolerated at the doses tested with no dose-limiting toxicities (DLTs) reported. This is the first publication of the clinical pharmacology profile of a CAR-T cell therapy in SCLC, with encouraging cellular kinetics data supporting the potential for CAR-T cell therapy in solid tumor space."

CAR T-Cell Therapy • Journal • Hematological Disorders • Hematological Malignancies • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A phase 1 study of AMG 119, a DLL3-targeting, chimeric antigen receptor (CAR) T cell therapy, in relapsed/refractory small cell lung cancer (SCLC) (SITC 2022) - "Conclusions AMG 119 , the first CAR-T cell therapy for SCLC, was associated with a manageable safety profile and promising anti-tumor activity. Enrollment is currently paused but may resume."

IO biomarker • P1 data • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Subtype-specific targeting of cell surfaceome with CAR T therapies in small cell lung cancer (AACR 2023) - "Targeting SCLC cell surfaceome with cellular therapies have shown promising efficacy and tolerability in DLL3-targeting CAR T (AMG119) and Bispecific T-cell engager (tarlatamab)...Moreover, given that novel therapeutics are often tested in the relapsed setting, we tested target expressions in SCLC cell lines after treatment with cisplatin and etoposide (standard frontline chemotherapy for SCLC) to see if target levels change. This study demonstrated efficacy of CAR Ts targeting several cell surfaceome targets enriched in certain subtypes of SCLC. The data supports further investigation of a subtype-specific personalized treatment of SCLC using CAR T therapies against surfaceome targets."

IO biomarker • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • DLL3 • NCAM1 • NEUROD1 • NEUROD1 • POU2F3

DLL3 Targeting Agents (IASLC-WCLC 2019) - P1, P2, P3; "An active phase 3 trial of Rova-T in the maintenance setting (MERU) is ongoing (NCT03033511).Other DLL3-targeting therapies under active investigation include the bispecific T cell engager (BiTE) AMG 757 (NCT03319940), and a chimeric antigen receptor CAR-T AMG119 (NCT03392064). Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol 18, 42-51, doi:10.1016/S1470-2045(16)30565-4 (2017)."

IO biomarker • IO Companion diagnostic • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Targeting cancer stem cell pathways for lung cancer therapy. (PubMed, Curr Opin Oncol) - "The current review elucidates the characteristics and related regulating pathways of lung CSCs from essential to preclinical research. We retrospectively introduce an update on the clinical development of therapeutics targeting CSC-associated developmental signaling pathways and discuss the opportunities to target CSC-immune interactions in lung cancer."

Cancer stem cells • Journal • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=6; Suspended; Sponsor: Amgen; Trial completion date: Jan 2025 ➔ Jan 2026; Trial primary completion date: Jan 2025 ➔ Jan 2026

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • MRI

Phase 1 study of AMG119, a chimeric antigen receptor (CAR) T cell therapy targeting DLL3, in patients with relapsed/refractory small cell lung cancer (SCLC). (ASCO 2019) - P1; "AMG 119 is an adoptive cellular therapy that consists of a patient’s autologous T cells that have been genetically modified ex vivo to express a transmembrane CAR that targets DLL3 and redirects cytotoxic T cell specificity to DLL3-positive cells. The dose expansion phase will seek to confirm the MTCD or RP2CD and obtain further safety and efficacy data. Clinical trial information: NCT03392064"

Clinical • P1 data

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=6; Suspended; Sponsor: Amgen; Active, not recruiting ➔ Suspended

Clinical • Trial suspension • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Generation and evaluation of an FLT3 CAR-T cell therapy for the treatment of acute myeloid leukemia (AACR 2018) - "These results demonstrate the potential of using FLT3 CAR-T cell therapy for the treatment of AML."

CAR T-Cell Therapy • IO Biomarker • Acute Myelogenous Leukemia

Precision medicine for human cancers with Notch signaling dysregulation (Review). (PubMed, Int J Mol Med) - "Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs...Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. Integration of human intelligence, cognitive computing and explainable artificial intelligence is necessary to construct a Notch‑related knowledge‑base and optimize Notch‑targeted therapy for patients with cancer."

Journal • Acute Lymphocytic Leukemia • Breast Cancer • Desmoid Tumors • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Hepatology • HER2 Breast Cancer • Leukemia • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma • T Acute Lymphoblastic Leukemia • Thoracic Cancer

Allogene Therapeutics Presents Preclinical Findings Supporting an Allogeneic DLL3 CAR for Small Cell Lung Cancer and Development of an Inducible TurboCAR at the American Association for Cancer Research (AACR) Virtual 2020 Meeting (GlobeNewswire) - "Lead DLL3 candidates were tested in vivo and robust efficacy was observed in both subcutaneous and systemic models of SCLC. Additionally, while DLL3 RNA has normal tissue expression in the brain, pituitary and testis, toxicity studies using subcutaneous and intracranial tumor models showed no tissue damage in the brain or pituitary."

Preclinical • Oncology • Small Cell Lung Cancer

DLL3: an emerging target in small cell lung cancer. (PubMed, J Hematol Oncol) - "It is therefore being explored as a potential therapeutic target in SCLC. Here, we review the preclinical and clinical evidence for targeting DLL3 in SCLC and discuss several DLL3-specific therapies being developed for the treatment of SCLC: the antibody-drug conjugate rovalpituzumab tesirine, the bispecific T cell engager immuno-oncology therapy AMG 757, and the chimeric antigen receptor T cell therapy AMG 119."

Journal • Review • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

"Analyst offers Amgen a boost for its rival anti-BCMA BiTE, blemishing GSK as well as CAR-T rivals Celgene and bluebird https://t.co/TzpXxdhBQ7 $AMGN $GSK $CELG $BLUE" (@endpts)

AMG 757 (DLL3) + AMG 119 (DLL3) (CAR-T) (IASLC-LCTT 2020) - No abstract available

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Amgen; Trial completion date: Mar 2020 ➔ Jan 2025; Trial primary completion date: Mar 2020 ➔ Jan 2025

Clinical • Trial completion date • Trial primary completion date

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Amgen; Trial completion date: Jun 2021 ➔ Mar 2020; Trial primary completion date: Jun 2021 ➔ Mar 2020

Clinical • Trial completion date • Trial primary completion date

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=6; Active, not recruiting; Sponsor: Amgen; Recruiting ➔ Active, not recruiting; N=41 ➔ 6

Clinical • Enrollment change • Enrollment closed

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov) - P1; N=41; Recruiting; Sponsor: Amgen; Trial completion date: Aug 2020 ➔ Jun 2021; Trial primary completion date: Aug 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date

Amgen showcases oncology pipeline at ASCO 2019 (Amgen Press Release) - "Amgen...announced that data from its oncology pipeline will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO)...Notable data from the Company's oncology pipeline include first-in-human data for investigational AMG 510...in patients with locally-advanced or metastatic KRASG12C mutant solid tumors...Updated results will also be presented from a Phase 1 dose escalation study evaluating investigational AMG 420....in patients with relapsed or refractory multiple myeloma."

Clinical data