“Designer Drug” Rociletinib Shows Encouraging Results in Patients with NSCLC and T790M Mutation

Alice Goodman

September 2015, Vol 6, No 8 - Emerging Therapies

Boston, MA—Rociletinib, a specially engineered third-generation EGFR inhibitor, is accumulating an impressive track record in early studies of non–small-cell lung cancer (NSCLC). The drug is specifically designed for use in patients with NSCLC and the T790M mutation, a heretofore patient population with unmet needs. T790M, the most common mutation associated with resistance to first-line EGFR-directed tyrosine kinase inhibitor (TKI) therapy, is present in 60% of patients with resistance to TKIs.

The phase 1/2 study of rociletinib, TIGER-X, demonstrated that T790M status can be accurately assessed in plasma, which can replace tissue biopsies in advanced NSCLC. The study showed that rociletinib can achieve good response rates and duration of response in patients with T790M; unexpectedly, approximately 33% of patients without the T790M mutation also responded to this third-generation targeted therapy.

Leena Gandhi, MD, PhD, a thoracic oncologist at Dana-Farber Cancer Institute, Boston, discussed these findings from TIGER-X at the 2015 Best of ASCO meeting in Boston.

TIGER-X showed responses for 243 patients who received 4 different doses of rociletinib—500 mg twice daily, 625 mg twice daily, 750 mg twice daily, or 1000 mg twice daily—who had the T790M mutation.

The best overall response rate (53%) was identical in patients with tissue-typed and plasma-typed disease; the overall disease control rate was 85% with tissue-typed disease and 82% with plasma-typed disease.

Although still immature, the progression-free survival was 10.3 months in patients with no brain metastases and 8 months in all patients.

“This study demonstrated that response rates by tissue typing versus plasma typing for T790M-positive status were essentially identical. This suggests that plasma T790M testing can be used to guide treatment instead of tissue samples. This is good news, because not all patients who progress on first-line TKI therapy are candidates for tissue rebiopsy, and it can be difficult to do rebiopsy in NSCLC,” Dr Gandhi noted.

Hyperglycemia was an unexpected treatment-related adverse event in early studies of rociletinib. A monitoring and treatment algorithm has been put in place, which has reduced the incidence of grade 3 and 4 hyperglycemia from 22% to 8% at the 500-mg twice-daily dosing.

The FDA has granted rociletinib a breakthrough therapy designation based on current data for the treatment of advanced T790M-positive NSCLC that is resistant to first-line EGFR therapy. Clovis Oncology submitted a new drug application for rociletinib on August 3, 2015. Phase 2, phase 3, and combination studies of rociletinib are now under way.

Another third-generation EGFR inhibitor, AstraZeneca’s AZD9291, is also being developed for T790M-positive NSCLC. This drug appears to have potent activity in the resistant setting and as first-line treatment, Dr Gandhi said.