AbbVie’s Drug Rova-T Shows Promise — But Not Enough — in SCLC

Small-cell lung cancer of a human, photomicrograph panorama as seen under the microscope, 200x zoom.

Experimental drug rovalpituzumab tesirine (Rova-2) was effective in treating patients with advanced small cell lung cancer (SCLC), according to data from a first-in-human clinical trial, presented at the American Society of Clinical Oncology (ASCO) meeting in Chicago.

And although the results are preliminary, that’s good news: Rova-2 could be the first treatment to make an impact on SCLC, which kills approximately 60,000 patients in the U.S. each year. There has been no change in survival rates for SCLC since the 1970s, according to Charles Rudin, a Memorial Sloan Kettering oncologist who led the study.

Rova-T targets the delta-like 3 (DLL3) protein, which is overexpressed in about two-thirds of SCLC tumors. The antibody-drug conjugate binds to DLL3 on the surface of tumor cells killing the detected cells, while salvaging normal tissue. Significantly, patients with the highest levels of DLL3 in their tumors responded best to the treatment.

“Rova-T seems to be the first targeted therapy to show efficacy in SCLC, and we may have identified DLL3 as the first predictive biomarker in this disease,” said Rudin.

The clinical trial included 74 patients with SCLC that had progressed after at least one course of therapy. Of 60 evaluable patients receiving Rova-T, 68 percent experienced disease stabilization and 18 percent experienced tumor shrinkage. And in the 26 patients whose tumors overexpressed DLL3, 39 percent responded to the therapy.

That puts the median overall survival rate at 5.8 months with 32 percent of the patients alive after a year of treatment. But that’s a month longer — 5.8-month median survival versus the 4.7-month historical average — according to Forbes’s Matthew Herper, who said, “Many on Wall Street are likely to find that 1-month survival benefit disappointing.” What’s more, Rova-T’s median survival was less than a combination of Bristol-Myers Squibb’s Opdivo and Yervoy, which showed 7.7 months median survival.

And that’s significant considering the price AbbVie paid: $5.8 billion upfront —and $4 billion reserved for drug approvals and sales — for the biotech startup, Stemcentrx, which manufactures Rova-T.

Next up will be confirmation in larger trials: Rova-T will be tested in a 154-patient study that will include patients with high levels of DLL3. Combination therapies of Rova-T and Opdivo are also being considered.

Side effects of Rova-T included fluid build-up in the heart or lungs, low platelet count, and skin reactions.