July 17, 2019 - Episode 1

FDA Approvals Sought in Urothelial Cancer and Myeloma, Orphan Drug Status in SCLC, and More


FDA approvals sought in urothelial cancer and multiple myeloma, orphan drug status granted in small cell lung cancer, encouraging findings in an ovarian cancer trial, and a Canadian approval in breast cancer.

Welcome to OncLive News Network! I’m Gina Columbus.

A biologics license application has been submitted to the FDA for enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic setting.

The application is based on findings from a cohort of patients enrolled on the single-arm, phase II EV-201 trial, in which the overall response rate was 44% with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer. This included a 12% complete response rate.

Additional results showed that the median overall survival was 11.7 months, the median progression-free survival was 5.8 months, and the median duration of response was 7.6 months.

Cohort 2 of the EV-201 trial continues to enroll patients.

Previously, the FDA granted the agent a breakthrough therapy designation in March 2018 for patients with locally advanced or metastatic urothelial cancer who experienced disease progression during or following checkpoint inhibitor therapy.


In multiple myeloma, a supplemental biologics license application has been submitted to the FDA for a new subcutaneous formulation of daratumumab for patients with the disease.

The sBLA is based on findings from the phase III COLUMBA study, which showed noninferiority in terms of efficacy versus the intravenous formulation of the CD38-targeted monoclonal antibody. Data also demonstrated that the subcutaneous version led to a reduction in treatment burden when compared with the standard version. The application also includes results from the ongoing, phase II PLEIADES trial.

In COLUMBA, results showed that the objective response rate was 41.1% with subcutaneous daratumumab versus 37.1% with the intravenous formulation, which met the criteria for noninferiority.

Additionally, the median duration per infusion dropped from more than 3 hours per infusion in the IV arm to 5 minutes with the subcutaneous version.

At a median follow-up of 7.46 months, the median progression-free survival was 6.1 months with IV daratumumab versus 5.6 months with the subcutaneous formulation. The 6-month overall survival rate was 83.0% versus 87.5% for the IV and subcutaneous formulations, respectively.


The FDA has granted an Orphan Drug Designation to durvalumab for the treatment of patients with small cell lung cancer.

The designation follows the announcement of the phase III CASPIAN trial data, in which the combination of durvalumab and standard etoposide and platinum-based chemotherapy showed a statistically significant and clinically meaningful improvement in overall survival compared with chemotherapy alone for patients with extensive-stage SCLC. Results of the study will be presented at an upcoming medical meeting.

AstraZeneca, the manufacturer of the PD-L1 inhibitor, previously stated that the safety and tolerability findings of the immunotherapy/chemotherapy combination were consistent with the safety profile of each agent alone.

The PD-L1 inhibitor is currently being evaluated in the phase III ADRIATIC trial, which is exploring durvalumab following concurrent chemoradiation therapy in patients with limited-stage SCLC.

*********************************** In ovarian cancer, niraparib as a maintenance treatment demonstrated a statistically significant improvement in progression-free survival compared with placebo in patients following first-line platinum-based chemotherapy, regardless of biomarker status, meeting the primary endpoint of the phase III PRIMA trial.

In the phase III, randomized, double-blind, placebo-controlled study, investigators compared maintenance niraparib with placebo in approximately 620 patients with stage III/IV ovarian cancer.

Those who had responded to first-line platinum-based chemotherapy were randomized 2:1 to receive either niraparib at a starting dose of 200 mg daily in those with baseline weight more than 77 kg or a platelet count less than 150K/μL and 300 mg in all other patients, or placebo. The safety and tolerability profile of the PARP inhibitor was also found to be consistent with prior clinical studies. Full findings of the PRIMA trial will be presented at an upcoming medical meeting.

The FDA approved niraparib for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, in March 2017.


Health Canada has approved neratinib for the extended adjuvant treatment of patients with early-stage, hormone receptor—positive, HER2-overexpressed/amplified breast cancer within 1 year after completing trastuzumab-based adjuvant therapy.

The approval is based on findings from the phase III ExteNET trial, in which the 2-year invasive disease-free survival rate was 95.3% in those who received neratinib compared with 90.8% in the placebo arm for this patient population.

At the 2-year follow-up, additional results showed that treatment with neratinib led to a 51% reduction in the risk invasive disease recurrence or death at 2 years compared with placebo. Updated findings showed that at a median follow-up of 5.2 years, the iDFS rate with neratinib was 90.2% compared with 87.7% with placebo, leading to a 27% reduction in the risk of invasive disease recurrence or death.

Moreover, the longer-term data showed that the restricted mean iDFS was 56.5 months with neratinib versus 55.2 months with placebo.

The FDA approved neratinib in July 2017 for the extended adjuvant treatment of patients with early-stage, HER2-positive breast cancer following postoperative trastuzumab.


This week, we sat down with Dr John Gosney, of the Royal Liverpool and Broadgreen University Hospital NHS Trust, to discuss the changing landscape in molecular testing.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.