Universität zu Köln

Morgensztern, Daniel, Besse, Benjamin, Greillier, Laurent ORCID: 0000-0002-5807-9503, Santana-Davila, Rafael, Ready, Neal, Hann, Christine L., Glisson, Bonnie S., Farago, Anna F., Dowlati, Afshin, Rudin, Charles M., Le Moulec, Sylvestre, Lally, Satwant, Yalamanchili, Sreeni, Wolf, Juergen, Govindan, Ramaswamy and Carbone, David P. (2019). 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. Clin. Cancer Res., 25 (23). S. 6958 - 6967. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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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. Patients and Methods: 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 end-points 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Morgensztern, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Besse, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Greillier, Laurent UNSPECIFIED orcid.org/0000-0002-5807-9503 UNSPECIFIED Santana-Davila, Rafael UNSPECIFIED UNSPECIFIED UNSPECIFIED Ready, Neal UNSPECIFIED UNSPECIFIED UNSPECIFIED Hann, Christine L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Glisson, Bonnie S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Farago, Anna F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dowlati, Afshin UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudin, Charles M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Le Moulec, Sylvestre UNSPECIFIED UNSPECIFIED UNSPECIFIED Lally, Satwant UNSPECIFIED UNSPECIFIED UNSPECIFIED Yalamanchili, Sreeni UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Govindan, Ramaswamy UNSPECIFIED UNSPECIFIED UNSPECIFIED Carbone, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-125991
DOI:	10.1158/1078-0432.CCR-19-1133
Journal or Publication Title:	Clin. Cancer Res.
Volume:	25
Number:	23
Page Range:	S. 6958 - 6967
Date:	2019
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	1557-3265
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 2ND-LINE TREATMENT; OPEN-LABEL; DRUG; TOPOTECAN; TRIAL; IRINOTECAN/CISPLATIN; ETOPOSIDE/CISPLATIN; THERAPY; DLL3 Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12599