436PD - Preliminary Safety and Efficacy of Rovalpituzumab Tesirine in Patients With Delta-Like Protein 3-Expressing Advanced Solid Tumors

Date 11 September 2017
Event ESMO 2017 Congress
Session Endocrine and neuroendocrine tumours
Topics Clinical research
Endocrine Cancers
Basic Scientific Principles
Presenter Rahul Aggarwal
Citation Annals of Oncology (2017) 28 (suppl_5): v142-v157. 10.1093/annonc/mdx368
Authors R. Aggarwal1, A. Mansfield2, H. Beltran3, A.F. Farago4, C.L. Hann5, F. Kaye6, K. Lewis7, J. Niu8, S. Richey9, D. Smith10, H.P. Soares11, A. Spira12, M. Taylor13, S.N. Waqar14, S. Lally15, M. Rossi15, L. Saunders15, S.J. Dylla15, E. Kavalerchik15, L. Anthony16
  • 1Division Of Hematology/oncology, University of California at San Francisco, 94143 - San Francisco/US
  • 2Division Of Medical Oncology, Mayo Clinic, 55905 - Rochester/US
  • 3Division Of Hematology And Medical Oncology, Weill Cornell Medical College, 10021 - New York/US
  • 4Thoracic Oncology, Massachusetts General Hospital, Boston/US
  • 5Oncology, Johns Hopkins University, 21231 - Baltimore/US
  • 6Division Of Hematology And Oncology, University of Florida, Gainesville/US
  • 7Division Of Medical Oncology, University Of Colorado, 80045 - Aurora/US
  • 8Hematology/oncology, Banner MD Anderson Cancer Center, Gilbert/US
  • 9Hematology, Texas Oncology, Fort Worth/US
  • 10Oncology/hematology, Compass Oncology, Vancouver/US
  • 11Medical Oncology, Moffitt Cancer Center, Tampa/US
  • 12Oncology, Virginia Cancer Specialists Research Institute, Fairfax/US
  • 13Medical Oncology, Oregon Health and Science University, Portland/US
  • 14Division Of Oncology, Washington University School of Medicine, St. Louis/US
  • 15Clinical Development, AbbVie Stemcentrx LLC, South San Francisco/US
  • 16Division Of Medical Oncology, University of Kentucky Chandler Medical Center, Lexington/US



Delta-like protein 3 (DLL3) is an atypical Notch receptor family ligand expressed in high-grade neuroendocrine carcinomas (NECs), but not in normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3. A Phase 1 study of Rova-T in small cell lung cancer showed encouraging antitumor activity in patients (pts) with DLL3 expression, and was well-tolerated1. Rova-T may also be active in other DLL3-expressing tumors.


This is a Phase 1/2, open-label, multicenter study (NCT02709889) to determine safety and tolerability of Rova-T in 8 cohorts: malignant melanoma, medullary thyroid cancer (MTC), glioblastoma (GBM), large cell NEC (LCNEC), neuroendocrine prostate cancer (NEPC), high-grade gastroenteropancreatic NEC (GEP NEC), other NEC and other solid tumors. Eligible adults have a histologically confirmed, DLL3-expressing, advanced solid tumor relapsed/refractory to standard therapy, and no prior exposure to a pyrrolobenzodiazepine-based drug. A 3 + 3 dose escalation is used in each cohort, at doses 0.2-0.4 mg/kg of Rova-T administered intravenously on Day 1 of each 42-day cycle, and proceeding until a maximum tolerated dose (MTD) is determined. A 2-stage design will be used for disease-specific expansion cohorts.


As of 3 April 2017, 31 pts (2 melanoma, 2 MTC, 3 GBM, 3 LCNEC, 3 NEPC, 3 GEP NEC, 10 other NEC, 5 other solid tumor) have been treated (26 pts at 0.2 mg/kg, 5 pts at 0.3 mg/kg Rova-T). The MTD has not been reached. Twenty-six pts (84%) had an adverse event (AE), and only 3/31 pts (10%) had a Grade 3+ AE deemed to be related to Rova-T. Common AEs were fatigue (32%), nausea (29%), and constipation (23%). Four pts had serosal effusions, 2 (6%) of which were assessed to be drug-related, and 3 pts (10%) had adverse skin reactions. Ten pts (32%) discontinued treatment, 5 for progressive disease and 4 due to AEs. Eleven pts have had post-baseline tumor assessments, and anti-tumor activity has been observed in multiple disease cohorts.


Preliminary safety and efficacy data of Rova-T warrant continued study in these disease populations, and will be updated at time of presentation. 1. Rudin et al., Lancet Oncol 2016.

Clinical trial identification


Legal entity responsible for the study

AbbVie Stemcentrx


AbbVie Stemcentrx


A. Mansfield: Consulting to Genentech, BMS and Trovagene with honoraria provided to institution. H. Beltran, K. Lewis: Research funding from AbbVie Stemcentrx. A.F. Farago: Consulting or advisory role for AbbVie, Pharmamar, Merrimack Pharmaceuticals, Takeda, Intervention Insights. Honorarium from Foundation Medicine. C.L. Hann: Advisory board for AbbVie Stemcentrx and BMS. Research funding from GlaxoSmithKline and Merrimack Pharmaceuticals. S. Richey: Employee of Texas Oncology. Consulting or advisory role for Exelixis, Pfizer, Prometheus and Sanofi. Research funding from Novartis, BMS, Eisai, Genentech/Roche, GSK, and AbbVie. D. Smith: Research funding from US Oncology. H.P. Soares: Advisory board for Cornerstone Pharmaceuticals. Research funding from Novartis. Consultant fees/honoraria for Ipsen. A. Spira: Consultant for AbbVie. Research funding from AbbVie (to institution). S. Lally, M. Rossi, L. Saunders, S.J. Dylla, E. Kavalerchik: Employee of AbbVie Stemcentrx and may own stock. L. Anthony: Research funding from AbbVie Stemcentrx, Lexicon Pharmaceuticals, Novartis, Markey Cancer Center Foundation. All other authors have declared no conflicts of interest.