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Marie-Anne Damiette Smit
OA13 - Therapeutics and Radiation for Small Cell Lung Cancer (ID 927)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 203 BD
OA13.02 - Two Novel Immunotherapy Agents Targeting DLL3 in SCLC: Trials in Progress of AMG 757 and AMG 119 (ID 14538)
10:40 - 10:50 | Author(s): Marie-Anne Damiette Smit
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by initial response to chemotherapy and radiotherapy followed by relapse or progression with chemoresistant disease. Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand that is specifically upregulated in SCLC. IHC profiling of tumor samples showed DLL3 expression in 86% of SCLC tumors and minimal expression in normal tissue.
We are conducting clinical trials of two novel immunotherapy agents that target DLL3. AMG 757 is a half-life extended bispecific T cell engager (BiTE®) antibody construct that is designed to transiently crosslink DLL3-positive SCLC cells to CD3-positive T cells and induce T cell–mediated tumor cell lysis and concomitant T cell proliferation. 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 chimeric antigen receptor that targets DLL3 on the surface of SCLC cells. Both AMG 119 and AMG 757 showed potent killing of SCLC cell lines with a broad range of DLL3 expression in vitro and inhibition of tumor growth in the SHP-77 human SCLC xenograft model in vivo. AMG 757 was well tolerated in a preclinical multi-dose GLP toxicology study, with no evidence of tissue damage at weekly doses as high as 4.5 mg/kg.
NCT03319940 is an open label, phase 1 study evaluating the safety, tolerability and pharmacokinetics of AMG 757 that will initially enroll adult patients with SCLC who have progressed or recurred following platinum-based chemotherapy. Key inclusion criteria: ECOG PS 0–2, life expectancy ≥12 weeks, at least 2 measurable lesions per modified RECIST 1.1 criteria, and adequate organ function. The study will later enroll patients with extended disease SCLC with ongoing clinical benefit following no more than 6 cycles of first-line platinum-based chemotherapy. AMG 757 will be administered as an intravenous infusion once every 2 weeks.
NCT03392064 is an open-label, phase 1 study evaluating the safety, tolerability and efficacy of AMG 119 in adult patients with SCLC whose disease has progressed or recurred after at least one platinum-based regimen. Key inclusion criteria: ECOG PS 0–1, at least 2 measurable lesions per modified RECIST 1.1 criteria, no evidence of CNS metastasis, and adequate organ function. AMG 119 will be administered as a one-time intravenous infusion.
Both of these studies are currently enrolling patients. For more information, please contact Amgen Medical Information: [email protected]
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