Rova-T Underperforms in Phase II SCLC Trial

Rovalpituzumab Tesirine (Rova-T) delivered disappointing preliminary results in the third-line setting for patients with relapsed/refractory small cell lung cancer with high DLL3 expression.

Mike Severino, MD

Rovalpituzumab Tesirine (Rova-T) delivered disappointing preliminary results in the third-line setting for patients with relapsed/refractory small cell lung cancer (SCLC) with high DLL3 expression, according to findings from the single-arm, phase II TRINITY trial.

Per investigator assessment, the DLL3-targeted antibody-drug conjugate had a best overall response (BOR) rate of 29% (95% CI, 22-36), with BOR defined as a complete response (CR) or partial response (PR) at any time prior to receiving any subsequent anticancer therapy.1

The objective response rate (ORR) was 16% (95% CI, 11-22) according to the independent review committee (IRC), with ORR defined as CR or PR prior to receiving any subsequent anticancer therapy, with confirmation of CR or PR at least 28 days from the initial determination per RECIST v1.1. Also per the IRC, the median duration of response was 4.1 months (95% CI, 3.0-4.2). The median overall survival (OS) was 5.6 months (95% CI, 4.9-6.8), with an estimated 12-month OS rate of 17.5% (95% CI, 10.8-25.5).

The full results have been submitted for presentation at the 2018 ASCO Annual Meeting. Based on these findings, AbbVie, the manufacturer of the antibody-drug conjugate, announced that it will not seek accelerated approval from the FDA for use of the drug in third-line SCLC.

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

The multicenter, open-label, single-arm TRINITY trial included 177 patients with DLL3-expressing SCLC who had undergone at least 2 previous treatment regimens, at least 1 of which was a platinum-based regimen. The primary objective was an assessment of Rova-T’s efficacy of Rova-T as third-line and later treatment. Secondary objectives included assessment of safety and tolerability, pharmacokinetics, RECIST-assessed progression-free survival (PFS), duration of response, and clinical benefit rate.

The most common treatment-emergent adverse events (TRAEs) 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%).

The most common (≥5%) grade ≥3 severe toxicities were thrombocytopenia (11%), photosensitivity reaction (7%), and pleural effusion (5%).

The ongoing phase III MERU study (NCT03033511) is exploring Rova-T as maintenance therapy following first-line platinum-based chemotherapy in patients with extensive stage SCLC. The phase III TAHOE trial (NCT03061812) is comparing Rova-T with topotecan in patients with advanced or metastatic SCLC with high levels of DLL3 who have first disease progression during or following frontline platinum-based chemotherapy.

Rova-T previously demonstrated promising activity in a first-in-human, first-in-class, open-label phase I study.2 Eighty-two patients enrolled in the study at 10 US centers from July 2013 to August 2015. The population included 74 patients with SCLC and 8 with large-cell neuroendocrine carcinoma. All patients received at least 1 dose of Rova-T. The whole study cohort received a median of 2 doses (IQR 1-3; range 1-14).

Eleven of 60 assessable patients (18%) who received an active dose of Rova-T (0.2 mg/kg or 0.4 mg/kg every 3 weeks or 0.3 mg/kg or 0.4 mg/kg every 6 weeks) achieved a confirmed objective response, and 30 patients (50%) had stable disease. The median PFS was 2.8 months (95% CI, 2.5-4.0).

An exploratory analysis of available tumor tissue samples (n = 34) showed an overall response rate of 38% (n = 10) among 26 DLL3-high patients (tumor expression levels ≥50%) compared with 0% in DLL3-low patients. The median PFS was 4.3 months (95% CI, 2.8-5.6) in DLL3-high patients versus 2.2 months (95% CI, 1.3-2.5) in DLL3-low patients.

Of 65 patients with SCLC who were assessable for activity analyses and received any dose of Rova-T, 11 (17%) achieved a confirmed objective response, and 35 (54%) had stable disease. Thus, 46 patients (71%) achieved disease control.

Thirty-nine patients provided samples for exploratory analysis of DLL3 expression in tumor tissue. Of 29 assessable DLL3-high patients, 10 (35%) had a confirmed objective response and 26 (90%) achieved disease control. Of the 10 assessable patients defined as DLL3-low, none achieved a confirmed objective response, though 6 (60%) had disease control.

In an exploratory analysis, the median PFS was 4.5 months (95% CI, 3.0-5.4) for DLL3-high patients (based on 26 of 29 patients who had disease progression or died) and 2.3 months (95% CI, 1.3-3.3) for DLL3-low patients (based on 9 of 10 patients who had disease progression or died).

In the 68 patients treated with active dose levels of Rova-T, OS was 4.6 months (95% CI, 3.9-7.1). In an exploratory analysis of DLL3 expression, 29 patients in the DLL3-high subset had a median OS of 5.8 months (95% CI, 4.4-11.6); in 10 patients in the DLL3-low subset, the median OS was 2.7 months (95% CI, 1.2-10).

The 1-year OS rate was 18% (95% CI, 9-29) in patients treated at the active dose levels, 32% (95% CI, 15-49) in DLL3-high patients, and 0% in DLL3-low patients. A posthoc analysis of chemotherapy-sensitive versus refractory or resistant patients showed a 1-year OS rate of 21% in patients with resistant/refractory disease; the rates were 29% in DLL3-high patients and 0% in DLL3-low patients.

Twenty-eight (38%) patients reported ≥grade 3 TRAEs. Thrombocytopenia (11%) was the most often reported ≥grade 3 TRAE, followed by pleural effusion (8%) and increased lipase (7%).


  1. AbbVie. AbbVie announces results from phase 2 study evaluating rovalpituzumab tesirine (rova-t) for third-line treatment of patients with Dll3-expressing relapsed/refractory small cell lung cancer. Available at: Accessed March 22, 2018.
  2. Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017;18(1):42-51. doi:10.1016/S1470-2045(16)30565-4.