An Independent Data Monitoring Committee (IDMC) responsible for ongoing review of study data of the TAHOE study, a Phase III study evaluating Rovalpituzumab Tesirine or Rova-T as a second-line therapy for advanced small-cell lung cancer (SCLC), has recommended that enrollment be stopped.
Rova-T is an antibody-drug conjugate of ADC being developed by AbbVie.
The investigational drug is designed to targeting the cancer-stem cell-associated delta-like protein 3 (DLL3) , which is expressed in more than 80% of small-cell lung cancer (SCLC) patient tumors, where it is prevalent on tumor cells, including cancer stem cells, but not present in healthy tissue.
Rova-T combines a targeted antibody that delivers a cytotoxic agent directly to the DLL3-expressing cancer cells while minimizing toxicity to healthy cells. Rova-T is under investigation as a third-line treatment in SCLC.
The expression of DLL3 suggests Rova-T may be useful across multiple tumor types, including metastatic melanoma, glioblastoma multiforme and some prostate, pancreatic and colorectal cancers.
Rova-T is being investigated in multiple trials, including the TAHOE study. This study is a randomized, open-label, two-arm, Phase III trial assessing the efficacy, safety and tolerability of Rova-T 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.
The Data Monitoring Committee made the recommendation based on shorter overall survival in the Rova-T arm compared with the topotecan control arm.
For patients currently on treatment with Rova-T in TAHOE study, the IDMC recommended that investigators and patients make individual decisions as to whether or not to continue treatment based on the patients individual level of response.
The recommendation from the IDMC to halt enrollment applies only to the TAHOE study and does not impact other Rova-T clinical studies.
“Patients are our first priority and we are deeply grateful to the patients and physicians who participated in this trial,” said Michael Severino, MD, executive vice president, research and development and chief scientific officer, AbbVie. “We remain committed to discovering and developing transformative therapies for people living with cancer.”
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) – NCT03061812
 Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black K, Desai R, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015 Aug 26;7(302):302ra136. doi: 10.1126/scitranslmed.aac9459.
 ClinicalTrials.gov (2016). 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. Last accessed December 4, 2018.