After consulting with the U.S. Food and Drug Administration (FDA), AbbVie, a global research and development-based biopharmaceutical company, announced that the company 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.

“We continue to believe Rova-T has potential for patients with small cell lung cancer and other DLL3-expressing cancers,” said Mike Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie.

“Although the results from the study were not what we hoped for, we look forward to receiving data from the ongoing Phase III studies in the first- and second-line settings and remain committed to developing Rova-T for the treatment of patients with small cell lung cancer,” Severino added.


Rovalpituzumab Tesirine (Rova-T)
Rova-T is an investigational antibody-drug conjugate or ADC targeting the cancer-stem cell-associated delta-like protein 3 (DLL3)[1], which is expressed in more than 80 percent 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.[2]

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.[2] 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.[2]

TRINITY is a multicenter, open-label, single-arm, Phase II study of Rova-T in DLL3-expressing small cell lung cancer (SCLC) patients with relapsed/refractory (R/R) disease after receiving at least two previous regimens, including at least one platinum-based regimen. The primary objective was to investigate the efficacy of Rova-T as third-line and later treatment for R/R DLL3-expressing SCLC. Secondary objectives included assessment of safety and tolerability, pharmacokinetics, RECIST-assessed progression-free survival, duration of response and clinical benefit rate.

Summary of Investigator Assessed Best Overall Response Rate, Independent Review Committee (IRC) Assessed Objective Response Rate, Duration of Response and Overall Survival in Third-Line SCLC Patients with High DLL3 Expression (N = 177)*
DLL3 High 3L (N = 177)
Investigator Assessed Outcome
Best Overall Response Ratea (95% CI)29% (22%, 36%)
IRC Assessed Outcomes
Objective Response Rate (by RECIST criteria – v1.1)b (95% CI)16% (11%, 22%)
Duration of Objective Response (months)
Median (months) (95% CI)
4.1 (3.0, 4.2)
Overall Survival
Median (months) (95% CI)5.6 (4.9, 6.8)
Probability of Subjects Alive at 12 months (95% CI)c17.5% (10.8%, 25.5%)
*Data represent 74 percent of the TRINITY study population with high DLL3 expression
a Best overall response is defined as a subject with a response of complete response (CR) or partial response (PR) at any time prior to receiving any subsequent anticancer therapy. 
b Objective response is defined as a subject with a response of complete response (CR) or partial response (PR) prior to receiving any subsequent anticancer therapy, with confirmation of CR or PR at least 4 weeks (28 days) from the initial determination per RECIST v1.1.
c Based on Kaplan-Meier estimate.

Adverse events
In the study, the most common treatment-emergent adverse events were fatigue (38%), photosensitivity reaction (36%), pleural effusion (32%), edema peripheral (31%), decreased appetite (30%), nausea (26%), dyspnea (25%), thrombocytopenia (25%), constipation (22%), vomiting (17%), anemia (17%), hypoalbuminemia (16%), and cough (16%). Grade three and higher severe toxicities ≥ 5% were thrombocytopenia (11%), photosensitivity reaction (7%) and pleural effusion (5%).