Novel immune agent shows early promise in SCLC
medwireNews: AMG 757, a half-life extended, bispecific T-cell engager (BiTE®) immunotherapy directed against DLL3, has demonstrated tolerability and antitumor activity in patients with previously treated small-cell lung cancer (SCLC) in a phase 1 trial.
The results were presented at the IASLC 2020 World Conference on Lung Cancer by Taofeek Owonikoko, from Emory University in Atlanta, Georgia, USA.
Discussant Stephen Liu (Georgetown University, Washington, DC, USA) said that “AMG 757 is an important molecule,” with “[c]lear activity and durable responses,” but he also stressed the preliminary nature of these findings.
Liu pointed out that these data “reflect a selected patient population treated in experienced centers of excellence,” adding that it is not yet clear whether the agent can be “safely delivered in a community setting.”
Presenting the dose-escalation part of the first-in-human study of AMG 757, the study author explained that “BiTE molecules engage a patient’s own T cells to attack and eradicate cancer cells,” with the inhibitory Notch ligand DLL3 (delta-like ligand 3) serving as “a promising target as it is highly expressed in SCLC and minimally expressed in normal tissues.”
Fifty-two SCLC patients who had received one or more prior lines of systemic therapy, including at least one platinum-based chemotherapy regimen, were treated with intravenous AMG 757 at doses of 0.003–10.0 mg every 2 weeks, with or without a step dose.
Treatment-related adverse events (TRAEs) of any grade occurred in 79% of patients, with 23% experiencing events of grade 3 or worse. Only one participant discontinued the study drug due to a TRAE, and there was one dose-limiting toxicity, namely grade 5 pneumonitis.
The most common TRAE was cytokine release syndrome, in 44%, but there was only one grade 3 case; all the others were of grade 1 or 2 and none led to treatment discontinuation.
Among the 51 response-evaluable patients, confirmed partial responses were observed in seven patients – one each in the 0.3 and 1.0 mg target dose groups, three in the 3.0 mg, and two in the 10.0 mg groups – giving an objective response rate of 14%.
An additional 11 patients had stable disease, and thus the disease control rate was 37%.
Of note, 20% of the total study population completed at least 6 months of treatment, and four of the seven responders remained on treatment and had ongoing responses (median duration, 6.2 months) at data cutoff.
These data “support AMG 757 as the first half-life extended BiTE® immuno-oncology therapy with a favorable safety profile and a durable response profile” in relapsed or refractory SCLC, summarized Owonikoko, adding that “[d]ose optimization for monotherapy is ongoing.”
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