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Clin Cancer Res. 2019 Sep 10. doi: 10.1158/1078-0432.CCR-19-1133. [Epub ahead of print]

Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study.

Author information

1
Washington University, St. Louis, Missouri. danielmorgensztern@wustl.edu.
2
Gustave Roussy, Villejuif, France.
3
Paris-Sud University, Orsay, France.
4
Assistance Publique-Hôpitaux de Marseille, Aix Marseille University, Marseille, France.
5
University of Washington, Seattle, Washington.
6
Duke University Medical Center, Durham, North Carolina.
7
Johns Hopkins University, Baltimore, Maryland.
8
MD Anderson Cancer Center, Houston, Texas.
9
Massachusetts General Hospital, Boston, Massachusetts.
10
University Hospitals Case Medical Center, Cleveland, Ohio.
11
Memorial Sloan Kettering Cancer Center, New York, New York.
12
Institut Bergonié Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest, Bordeaux, France.
13
AbbVie Stemcentrx, South San Francisco, California.
14
Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany.
15
Washington University, St. Louis, Missouri.
16
Ohio State University, Columbus, Ohio.

Abstract

PURPOSE:

Although extensive-stage small-cell lung cancer (SCLC) is highly responsive to first-line therapy, virtually all patients develop resistance with short survival. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting delta-like 3 protein (DLL3). This open-label, single-arm, phase II study (TRINITY) assessed safety and efficacy of Rova-T in patients with DLL3-expressing SCLC in the third-line and beyond (3L+) setting.

EXPERIMENTAL DESIGN:

Patients with DLL3-expressing SCLC (determined by mouse antibody immunohistochemistry [IHC] assay), and ≥2 prior regimens, received 0.3 mg/kg Rova-T once every 6 weeks for two cycles. During study, a rabbit antibody IHC assay was developed and used for the final analysis, with DLL3-positive and DLL3-high defined as ≥25% and ≥75% of tumor cells positive for DLL3, respectively. The primary endpoints were objective response rate (ORR) and overall survival (OS).

RESULTS:

Among 339 patients enrolled, 261 (77%) had two prior lines of therapy and 78 (23%) had ≥3. DLL3-high and DLL3-positive tumors by rabbit IHC were seen in 238 (70%) and 287 (85%) patients, respectively. The remaining 52 (15%) were DLL3-negative only by rabbit IHC or had missing results. ORR was 12.4%, 14.3%, and 13.2% in all, DLL3-high, and DLL3-positive patients, respectively. Median OS was 5.6 months in all patients and 5.7 months in DLL3-high patients. The most common adverse events (AE) were fatigue, photosensitivity reaction, and pleural effusion. Grade 3-5 AEs were seen in 213 (63%) patients.

CONCLUSIONS:

Rova-T is the first targeted agent in SCLC to use DLL3, a novel biomarker. However, results demonstrate modest clinical activity in 3L+ SCLC, with associated toxicities.

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