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Phase I study of AMG 757, a delta-like ligand 3 (DLL3) targeting, half-life extended bispecific T-cell engager immuno-oncology therapy, in small cell lung cancer (SCLC)
Paz-Ares, L. Owonikoko, T. K. Johnson, M. Govindan, R. Izumi, H. Lai, V. Borghaei, H. Boyer, M. Boosman, R. J. Hummel, H. D.
Paz-Ares, L.
Owonikoko, T. K.
Johnson, M.
Govindan, R.
Izumi, H.
Lai, V.
Borghaei, H.
Boyer, M.
Boosman, R. J.
Hummel, H. D.
Citations
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Abstract
Background: AMG 757 simultaneously binds DLL3 on SCLC cells and
CD3 on T cells leading to T cell- mediated tumor lysis. Data from an
ongoing phase I study of AMG 757 in SCLC are reported.
Methods: Safety and efficacy were evaluated in a phase I trial of
AMG 757 for patients (pts) with relapsed/refractory SCLC after >= 1
platinum-based regimen (NCT03319940). AMG 757 was administered
intravenously (9 dose levels (DLs); dose range: 0.003−30 mg q2w, ±
step dosing).
Results: As of 03 Nov 2020, 52 pts (median age, 64 [32−80] y; median
prior lines of therapy, 2 [1−6]) were enrolled. 79% (41/52) of pts
reported treatment (tx)-related adverse events (TRAEs) (Grade [Gr] >=
2, 29/52 [56%], Gr >= 3, 12/52 [23%], Gr >= 4, 4/52 [8%]). TRAEs
accounted for 1 tx discontinuation and 1 death (Gr 5 pneumonitis, DL,
0.3 mg). Cytokine release syndrome (CRS; 44%; Lee criteria (2014): Gr
2, 5/52 [10%], Gr 3, 1/52 [2%], no Gr >= 4) was the most common
TRAE and typically occurred in cycle 1. Median time to onset of CRS was
9 (3−52) h following an AMG 757 dose; median duration was 60
(3−197) h. Fever (31%), tachycardia (19%), and nausea (14%) were the
most common CRS-related symptoms. Significant increases in cytokine
(IL-8, MCP-1, IFN-g, IL-10, IL-6, MIP-1a, MIP-1b, TNF-a) levels from
baseline in the 24 h following the first AMG 757 dose in cycle 1 were
observed in pts experiencing CRS vs. pts who did not experience CRS
symptoms. CRS did not result in tx discontinuation or deaths and was
managed with supportive care, corticosteroids, and/or anti-IL-6R. 14%
(7/51) of pts achieved a confirmed partial response (PR) (modified
RECIST 1.1) in 4 DLs (0.3 mg [8% of PR], 1 mg [13%], 3 mg [33%], and
10 mg [20%]). Stable disease was seen in 24% (12/51). Median time to
response was 1.8 months; the estimated duration of response was > 6
months in 83% (95% CI: 27%, 98%) of pts with a confirmed PR. An
unconfirmed PR was noted in an additional pt (30 mg DL).
Conclusions: AMG 757 showed an acceptable safety profile and
preliminary evidence for efficacy in pts with SCLC. The most common TRAE—CRS—occurred early in the dosing cycle, did not recur, was
typically mild in severity, and manageable. The maximum tolerated dose
has not been reached. Dose-finding for monotherapy is ongoing.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Paz-Ares L, Owonikoko TK, Johnson M, Govindan R, Izumi H, Lai V, et al. 48MO Phase I study of AMG 757, a delta-like ligand 3 (DLL3) targeting, half-life extended bispecific T-cell engager immuno-oncology therapy, in small cell lung cancer (SCLC). Journal of Thoracic Oncology. 2021 Apr;16(4):S720–1.