Updated results from a phase 1 study of AMG 757, a half-life extended bispecific T-cell engager (BiTE) immuno-oncology therapy against delta-like ligand 3 (DLL3), in small cell lung cancer (SCLC).

• DOI: 10.1200/jco.2021.39.15_suppl.8510
• Publication Date: 2021-06-02T14:47:40Z
• Authors: Taofeek K. Owonikoko; Stéphane Champiat; Melissa Lynne Joh...; Ramaswamy Govindan; Hiroki Izumi; W. Victoria Victo...; Hossein Borghaei; Michael J. Boyer; Rene J. Boosman; Horst-Dieter Hummel; Fiona Helen Black...; Noemi Reguart; Afshin Dowlati; Yiran Zhang; Sujoy Mukherjee; Mukul Minocha; Yanchen Zhou; Aditya Shetty; Nooshin Hashemi S...; Luis G. Paz-Ares
• Keywords: Discontinuation; Cytokine Release Syndrome

8510 Background: DLL3, an inhibitory Notch ligand, is a promising target as it highly expressed in SCLC compared to normal tissue. AMG 757, half-life extended BiTE immuno-oncology therapy, binds DLL3 on tumor cells and CD3 T cells, leading cell-dependent killing of tumors. Results from the first nine dosing cohorts showing preliminary efficacy 757 (confirmed partial response [PR], 14% pts) were previously presented. Here, updated safety, efficacy, pharmacokinetic data 10 ongoing phase 1 study are reported (NCT03319940). Methods: (0.003–100 mg) was administered IV every 2 weeks ± step dosing. Eligible patients (pts) had that progressed after ≥1 platinum-based regimen. Antitumor activity assessed by modified RECIST 1.1. Results: As 11 Jan 2021, 64 pts enrolled at dose levels (DLs; 0.003–100 received available for analyses. Median age (range, 32–80) y; 63 (98%) ECOG PS 0–1 median number prior lines therapy 1–6), with 28 (44%) receiving PD-1/PD-L1 therapy. treatment duration 6 0.1–71) wk. Treatment-related AEs occurred 53 (83%): 16 (25%) ≥ grade (G) 3, 4 (6%) ≥G4, (2%) G5 (pneumonitis; DL5 [0.3 mg]). led discontinuation pt (G3 encephalopathy, DL10 [100 Cytokine release syndrome (CRS; graded per Lee 2014 criteria) 27 (42%): G2 7 (11%), ≥G3 (2%). CRS presented mainly fever (31%), tachycardia (17%), nausea (13%), fatigue (9%), hypotension (9%). usually reversible managed supportive care, corticosteroids, and/or anti-IL-6R. did not lead any discontinuations. Sixty treated across DLs, follow-up 4.2 0.2–18.6) mo, evaluated efficacy. Confirmed PR all DLs 8/60 5/8 (63%) achieving unconfirmed 100 mg (DL10). The time 1.7 1.2–3.7) mo. estimated >6 months 71% (95% CI: 26, 92) PR. Disease control rate 43%, shrinkage 23/60 (38%). serum exposures increased approximately proportionally within range. Conclusions: has acceptable safety profile doses up mg. Responses rapid durable. Encouraging anti-tumor seen ranges, highest DL. ongoing; data, including rates response, will be Clinical trial information: NCT03319940.