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AbbVie has officially ended its rovalpituzumab tesirine (Rova-T) research and development program, which was exploring the antibody-drug conjugate in patients with small cell lung cancer.
AbbVie has officially ended its rovalpituzumab tesirine (Rova-T) research and development program, which was exploring the antibody-drug conjugate in patients with small cell lung cancer (SCLC).1
The decision follows topline results from the double-blind randomized phase III MERU trial, which showed that Rova-T did not demonstrate an overall survival (OS) benefit versus placebo as a maintenance therapy following first-line, platinum-based chemotherapy in patients with SCLC. AbbVie reported in press release that the MERU is trial being closed.
"Small cell lung cancer continues to be one of the most difficult-to-treat cancers where there is a significant need for transformative therapies. We are disappointed with this outcome for the patients who suffer from this disease," Margaret Foley, MD, vice president, global head of solid tumor development, AbbVie, said in the press release. "We remain committed to researching and developing other therapies with the potential to transform care for patients with small-cell lung cancer and other malignancies."
Rova-T is an investigational antibody-drug conjugate targeting delta-like protein 3 (DLL3), which is expressed in more than 80% of SCLC tumors.
AbbVie previously reported in December 2018 that the phase III TAHOE trial evaluating second-line Rova-T as a treatment for patients with SCLC had stopped enrollment as recommended by an Independent Data Monitoring Committee. The committee’s recommendation was based on a shorter OS reported in the Rova-T arm compared with the control arm of topotecan.
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 had first disease progression during or following frontline platinum-based chemotherapy. A total 600 patients were expected to enroll.
Prior to the TAHOE results, disappointing data were reported from the phase II TRINITY trial, in which Rova-T was explored as a third-line treatment in relapsed/refractory high DLL3-expressing SCLC.2
Per investigator assessment in TRINITY, Rova-T had a best overall response rate (ORR) 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 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).
Going forward, AbbVie plans to concentrate its research and development efforts on other established and investigational agents in its oncology portfolio.