Phase III Trial Evaluating Rova-T in Small Cell Lung Cancer Put on Hold

The phase III TAHOE trial evaluating rovalpituzumab tesirine as a second-line treatment for&nbsp;patients with advanced small cell lung cancer has been put on hold, based on a recommendation from an&nbsp;Independent Data Monitoring Committee, according to AbbVie, the developer of the investigational antibody-drug conjugate.<br /> &nbsp;

Michael Severino, MD

The phase III TAHOE trial (NCT03061812) investigating rovalpituzumab tesirine (Rova-T) as a second-line treatment for patients with advanced small cell lung cancer (SCLC) has been put on hold, based on a recommendation from an Independent Data Monitoring Committee (IDMC), according to AbbVie, the developer of the investigational antibody-drug conjugate.1

The recommendation was made due to a shorter overall survival (OS) reported in the Rova-T arm compared with the control arm of topotecan therapy. The committee suggested that investigators and their patients who are currently enrolled on TAHOE and receiving Rova-T treatment make individual decisions as to whether or not treatment should be continued based on patient level response. The IDMC’s recommendation does not impact other ongoing Rova-T clinical trials outside of TAHOE.

"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."

Rova-T is an investigational antibody-drug conjugate targeting delta-like protein 3 (DLL3), which is expressed in more than 80% of SCLC tumors. The open-label, two-arm, randomized, phase III TAHOE trial was evaluating the efficacy, safety, and tolerability of Rova-T versus topotecan in patients with advanced or metastatic SCLC with high levels of DLL3 and who have first disease progression during or following frontline platinum-based chemotherapy. A total 600 patients were expected to enroll.

Patients were randomized to receive Rova-T intravenously (IV) on day 1 of a 42-day cycle for 2 cycles or topotecan IV on days 1 through 5 of each 21-day cycle. The primary endpoint was OS, and secondary endpoints included objective response rate (ORR), change from baseline of the physical functioning scale score QlQ-C15-PAL, progression-free survival, duration of response, and clinical benefit rate.

To be eligible for enrollment, patients must have had histologically or cytologically confirmed advanced or metastatic SCLC with documented first disease progression during or following frontline platinum-based chemotherapy, DLL3 expression ≥75% of tumor cells, measurable disease by RECIST v.1.1, an ECOG performance status of 0 or 1, and recovery to grade 0 or 1 of any clinically significant toxicity, except alopecia, prior to study treatment. Those with a history of cerebral vascular event, unstable angina, myocardial infarction; leptomeningeal metastases; more than 1 prior therapy for SCLC; a serious infection within 2 weeks prior to randomization; a history of active malignancies; or prior exposure to topotecan, irinotecan, or any other topoisomerase I inhibitors were excluded from participation on the study.

This news follows that of the single-arm, phase II TRINITY trial (NCT02674568), in which Rova-T as a third-line treatment in relapsed/refractory high DLL3-expressing SCLC showed disappointing preliminary results.2

Per investigator assessment, Rova-T had a best overall response rate of 29% (95% CI, 22%-36%), which was defined as a complete response (CR) or partial response (PR) at any time prior to receiving any subsequent anticancer therapy.

The ORR was 18.0% (95% CI, 14.1%-22.5%) in the overall population 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. In the high-DLL3—expressing cohort, the ORR was 19.7% (14.9%-25.4%)

Overall, the median duration of response per IRC was 4.1 months (95% CI, 3.0-4.2), and the median overall survival (OS) was 5.6 months (95% CI, 4.9-6.8). This was similar in the DLL3-high cohort, which was a median OS of 5.7 months (95% CI, 4.9-6.7). Most patients in the DLL3-high group achieved stable disease or better.

Serious treatment-related adverse events (TRAEs) occurred in 30% of all patients, and 40% of patients experienced a grade ≥3 AE from Rova-T. Five percent of patients (n = 16) with TRAEs discontinued, 9% (n = 29) had their doses interrupted, and 9% (n = 32) had dose reductions. There were 10 treatment-related deaths, which included generalized edema (n = 2), pneumonitis (n = 2), ascites (n = 1), drug-induced liver injury (n = 1), pleural effusion (n = 1), pneumothorax (n = 1), respiratory failure (n = 1), and sepsis (n = 1).

Rova-T is also being evaluated in the phase III MERU trial (NCT03033511), which is looking at the antibody-drug conjugate as maintenance therapy following frontline platinum-based chemotherapy in patients with extensive-stage SCLC. In addition, phase I studies are also exploring Rova-T in combination with chemotherapy, nivolumab (Opdivo), and nivolumab plus ipilimumab (Yervoy).


  1. Phase 3 Trial of Rova-T as Second-line Therapy for Advanced Small-Cell Lung Cancer (TAHOE Study) Halted. AbbVie. Published December 5, 2018. Accessed December 6, 2018.
  2. Carbone DP, Morgensztern D, Le Moulec S, et al. Efficacy and safety of rovalpituzumab tesirine (Rova-TTM) in patients with DLL3-expressing, &ge;3rd line small cell lung cancer: results from the phase 2 TRINITY study.J Clin Oncol. 2018;36 (suppl; abstr 8507). doi: 10.1200/JCO.2018.36.15_suppl.8507.