An anti-DLL3 bispecific T-cell engager (BiTE®) demonstrated antitumor activity with an acceptable safety profile, according to interim results of a phase 1 study presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).

The following article features coverage from the Society of Immunotherapy of Cancer (SITC) 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

DLL3 is an inhibitory Notch ligand that is expressed highly by SCLC tumor cells, but is expressed at low levels by normal tissue.

This first-in-human, open-label, phase 1 study treated 40 patients with previously treated SCLC with AMG 757 of increasing doses in a dose-escalation phase followed by a dose-expansion phase. The primary endpoint was safety and tolerability and determining the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and antitumor activity.

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At baseline, the median age for patients was 64 years. Fifteen percent of patients were current smokers and 68% were former smokers. The majority of patients had 1 to 2 prior lines of therapy (70%). Previous programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) blockade was received by 43% of patients.

At an interim analysis, the objective response rate was 16%, and all were partial responses. The disease control rate was 45% at 4 weeks. During a median follow-up of 8.8 months, “5 of the 6 patients with a partial response are still receiving therapy and their responses are ongoing,” Hossein Borghaei, DO, MS, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, and presenter of the study, said.

Treatment-related adverse event (TRAEs) occurred among 80% of patients including 1 grade 5 pneumonitis. The most common TRAEs of any grade included cytokine release syndrome (CRS) among 43% of patients, followed by pyrexia, fatigue, nausea, and anemia. One patient discontinued treatment due to TRAEs.

CRS primarily occurred during the first cycle and did not recur thereafter, and was successfully managed by supportive care and prophylactic corticosteroids.

Dr Borghaei concluded that “AMG 757 is the first half-life–extended BiTE immunotherapy to show an acceptable safety profile and encouraging clinical activity in patients with relapsed/refractory SCLC.” He noted that the MTD was not reached and dose optimization was ongoing.

Disclosures: The presenting author disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original presentation.

Read more of Cancer Therapy Advisor‘s coverage of the SITC 2020 meeting by visiting the conference page.


Borghaei H, Boyer M, Johnson M, et al. AMG 757, a half-life extended bispecific T-cell engager (BiTE) immune therapy against DLL3 in SCLC: phase 1 interim results. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 359. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.