News - AMG 119 - LARVOL VERI

4ms

A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC (clinicaltrials.gov)

P1, N=6, Suspended, Amgen | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2027 --> Jan 2028

4 months ago

Trial completion date • Trial primary completion date

AMG 119

over2years

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.

over 2 years ago

Review • Journal

DLL3 (Delta Like Canonical Notch Ligand 3)

Rova-T (rovalpituzumab tesirine) • Imdelltra (tarlatamab-dlle) • AMG 119

over2years

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.

over 2 years ago

Journal • CAR T-Cell Therapy

DLL3 (Delta Like Canonical Notch Ligand 3)

AMG 119

almost3years

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.

almost 3 years ago

IO biomarker

DLL3 (Delta Like Canonical Notch Ligand 3) • NCAM1 (Neural cell adhesion molecule 1) • POU2F3 (POU Class 2 Homeobox 3) • ASCL1 (Achaete-Scute Family BHLH Transcription Factor 1) • NEUROD1 (Neuronal Differentiation 1)

DLL3 expression • NCAM1 expression • NCAM1 overexpression

cisplatin • etoposide IV • Imdelltra (tarlatamab-dlle) • AMG 119

3years

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.

3 years ago

Journal

DLL3 (Delta Like Canonical Notch Ligand 3)

DLL3 positive

AMG 119

over3years

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.

over 3 years ago

P1 data • IO biomarker

DLL3 (Delta Like Canonical Notch Ligand 3)

DLL3 expression

AMG 119

over5years

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.

over 5 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • FLT3 (Fms-related tyrosine kinase 3) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • NOTCH1 (Notch 1) • FGFR (Fibroblast Growth Factor Receptor) • CD19 (CD19 Molecule) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CCND1 (Cyclin D1) • CD79B (CD79b Molecule) • HGF (Hepatocyte growth factor) • ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1) • TNFA (Tumor Necrosis Factor-Alpha) • TNFRSF17 (TNF Receptor Superfamily Member 17) • NOTCH2 (Notch 2) • DLL3 (Delta Like Canonical Notch Ligand 3) • CD44 (CD44 Molecule) • NOTCH3 (Notch Receptor 3) • NOTCH4 (Notch 4) • RAC1 (Rac Family Small GTPase 1) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • FGF (Fibroblast Growth Factor) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

NOTCH1 mutation

Rova-T (rovalpituzumab tesirine) • Ogsiveo (nirogacestat) • AL101 • AMG 119 • dilpacimab (ABT-165)