Target DLL3 (delta-like 3) | delta like canonical Notch ligand 3
International Nonproprietary Name Rovalpituzumab tesirine
INN Number 10141
INN Proposed / List and Year 113 / 2015
INN Recommended / List and Year 75 / 2016
Common name / Synonyms Rova-T,
Developer Stemcentrx (now part of AbbVie)
Clinical domain Oncology
Clinical indication Cancers, small cell lung (SCLC)
Development status Phase I
On August 29, 2019, AbbVie confirmed that it discontinued the research and development program for Rovalpituzumab Tesirine (Rova-T).
A phase I study to evaluate the effect of rovalpituzumab tesirine on cardiac ventricular repolarization in subjects with small cell lung cancer (SCLC). (update September 2018)
A phase II long-term, extension study is to provide ongoing safety and efficacy follow-up of subjects who participated in a rovalpituzumab tesirine study that has completed the primary analysis and that is closing (update December 2019)
A phase II study study is to determine the efficacy of rovalpituzumab tesirine as a third-line and later treatment for participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer (SCLC) (update November 2019)
A single-arm, open-label phase III study to assess the overall safety of rovalpituzumab tesirine in participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer by evaluating the frequency of high grade (>= Grade 3) select treatment-emergent adverse events (TEAEs) (update December 2018)
A phase I/II study to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors. (September 2019).
A phase I study to test the effect of rovalpituzumab tesirine in the frontline treatment of small cell lung cancer (SCLC) (March 2020)
A Japanese multicenter, open-label, dose-escalation phase I study. This is the first study to assess the safety and tolerability as well as explore the pharmacokinetics, pharmacodynamics and antitumor activity of rovalpituzumab tesirine in Japanese participants with advanced small cell lung cancer (SCLC). (update august 2018)
A phase I/II study is to assess the safety and tolerability of rovalpituzumab tesirine (SC16LD6.5) at different dose levels in patients with small cell lung cancer whose cancer has progressed or recurred following standard chemotherapy. Once a safe and tolerable dose is determined, the anti-cancer activity of SC16LD6.5 will be assessed by measuring the extent of tumor shrinkage. (update August 2018)
A phase I/II study is to assess the safety and efficacy of rovalpituzumab tesirine administered in combination with nivolumab or nivolumab and ipilimumab in participants with extensive-stage small cell lung cancer (SCLC).(update July 2020).
A randomized, open-label, 2-arm, Phase III study is to assess the efficacy, safety and tolerability of rovalpituzumab tesirine versus topotecan in participants with advanced or metastatic Small Cell Lung Cancer (SCLC) with high levels of delta-like protein 3 (DLL3) and who have first disease progression during or following front-line platinum-based chemotherapy. (update February 2020)
A phase III, randomized, double-blind, placebo-controlled, multinational, and multicenter study to evaluate the efficacy of rovalpituzumab tesirine as maintenance therapy following first-line platinum-based chemotherapy. (update December 2019).
An open-label, Phase I, dose-escalation study to determine the recommended Phase II dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of budigalimab. This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax (June 2020)
Regulatory decisions FDA Orphan drug designation for SCLC | December 22, 2015
UNII (FDA) UNII-P256HB60FF
Drug description Rovalpituzumab tesirine, also known as Rova-T or SC0001 is an anti-[DLL3 (delta-like ligand 3)], humanized monoclonal antibody conjugated , on an average of 2 cysteines, to the pyrrolobenzodiazepine (PBD) dimer SCX, via a cleavable (valine-alanine dipeptide as cathepsine B cleavage site) maleimide type linker containing a spacer PEG (n=8).
Origin clone species Mus musculus
Expression system CHO (Chinese Hamster Ovary) cells
Monoclonal Antibody (mAb) IgG1 - kappa SC16
Linker A cleavable (valine-alanine dipeptide as cathepsine B cleavage site) maleimide type linker containing a spacer PEG (n=8).
An average of 2 cysteinyl
Drug/Payload pyrrolobenzodiazepine (PDB) dimer SCX
Molecular Formula C78-H108-N10-O25-S
Molecular Weight 1617.8222
Clinical Trials A Study of Rovalpituzumab Tesirine to Study Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer - NCT02874664
A Long-Term Study of Rovalpituzumab Tesirine - NCT03543358
Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY) - NCT02674568
Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer - NCT03334487
Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors - NCT02709889
A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer - NCT02819999
A Study on the Safety and Tolerability of Rovalpituzumab Tesirine in Japanese Patients With Advanced, Recurrent Small Cell Lung Cancer - NCT03086239
Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer - NCT01901653
Expanded Access to Rovalpituzumab Tesirine - NCT03503890
A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer - NCT03026166
Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE) (TAHOE) - NCT03061812
A Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First- Line Platinum-Based Chemotherapy in Participants With Extensive Stage Small Cell Lung Cancer (MERU) (MERU) - NCT03033511
A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors - NCT03000257