Rovalpituzumab tesirine Terminated ADC

Antibody Information

Entry ID	2500
INN	Rovalpituzumab tesirine
Status	Terminated
Drug code(s)	SC16LD6.5
Brand name	Rova-T
mAb sequence source	mAb humanized
General Molecular Category	ADC
Format, general category	Full length Ab conjugate
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	Valine-alanine (Cleavable linker)
Ave. DAR	2 (Site-specific)
Conjugated/fused moiety	DNA binding, Pyrrolobenzodiazepine (PBD) D6.5
Discovery method/technology	None

Therapeutic information

Target(s)	DLL3
Indications of clinical studies	Small cell lung cancer
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Terminated at Phase 3
Status	Inactive
Start of clinical phase (IND filing or first Phase 1)	July 15, 2013
Start of Phase 2	January 15, 2016
Start of Phase 3	February 07, 2017
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	AbbVie
Licensee/Partner	None
Comments about company or candidate	Aug. 29, 2019: AbbVie announced that MERU, a Phase 3 trial evaluating Rova-T as a first-line maintenance therapy for advanced small-cell lung cancer (SCLC), demonstrated no survival benefit at a pre-planned interim analysis for patients receiving Rova-T as compared with placebo. The overall safety profile was generally consistent with that observed in previous studies. The MERU trial is being closed, and the Rova-T research and development program has been terminated. AbbVie will move forward prioritizing other development programs within its oncology pipeline. NCT03033511 Phase 3 MERU study has primary completion date in Nov 2019; NCT03061812 Phase 3 TAHOE study has primary completion date in Feb 2020. Results of TRINITY Phase 2 study in SCLC: results demonstrate modest clinical activity in 3L+ SCLC, with associated toxicities. (doi: 10.1158/1078-0432.CCR-19-1133) March 2018: AbbVie announced that after consulting with the U.S. Food and Drug Administration (FDA), it will not seek accelerated approval for Rova-T in third-line relapsed/refractory (R/R) small cell lung cancer (SCLC) based on magnitude of effect across multiple parameters in this single-arm study. The ongoing Phase III studies, MERU and TAHOE, will continue to investigate Rova-T in first- and second-line SCLC. NCT03334487 Phase 3 for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer Withdrawn (Strategic considerations). NCT03033511 and NCT03061812 Phase 3 studies recruiting as of May 27, 2017. Preclinical data published (Saunders et al Science Translational Medicine Aug 2015). NCT01901653 Phase 1/2 started in July 2013. Orphan drug designation in US and Australia.
Full address of company	North Chicago, Illinois, United States North America United States of America https://www.abbvie.com/

Description/comment

The drug, D6.5, is a very potent form of chemotherapy, specifically a DNA-damaging agent, that is cell cycle independent. The ADC is composed of a humanized monoclonal antibody, dipeptide linker, and pyrrolobenzodiazepine (PBD) dimer toxin with a drug-to-antibody ratio of 2.

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	Lack of efficacy, Safety issues