February 13, 2019 - Episode 1

FDA Approvals in Myeloma and aTTP, Priority Review Designations in RCC and HNSCC, and More


FDA approvals in multiple myeloma and acquired thrombotic thrombocytopenic purpura, priority review designations in renal cell carcinoma and head and neck squamous cell carcinoma, an ODAC meeting scheduled in multiple myeloma, and a review period extended in graft-versus-host disease.

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

The FDA has approved a split-dosing regimen of daratumumab for patients with multiple myeloma, providing physicians the option to split the first infusion of the CD38-directed monoclonal antibody over 2 consecutive days or complete in a single session.

The approval is based on findings from the phase Ib EQUULEUS trial, which demonstrated that the pharmacokinetic concentrations of daratumumab at 16 milogram per kilogram were comparable at the end of weekly dosing, regardless of whether it was a split-dose or a single infusion. The safety profiles were also similar across both dosing regimens.

This decision follows approvals in both Canada and the European Union in December 2018 for the daratumumab initial infusion split-dosing regimen.

At a median follow-up of 12.0 months in the international, randomized trial, the treatment-emergent adverse event profiles were similar across the overall population and in patients with lenalidomide-refractory disease. Findings also showed that the split and single daratumumab doses have similar pharmacokinetic profiles. Overall, the findings suggested that the split-dosing regimen is feasible and may improve patient convenience for initial dosing.


In thrombotic thrombocytopenic purpura, the FDA has approved the nanobody caplacizumab-yhdp, known as Cablivi, in combination with plasma exchange and immunosuppression for the treatment of adult patients with acquired disease. This has made it the first FDA-approved therapy indicated for this patient population.

The approval is based on data from the pivotal phase III HERCULES trial, in which the caplacizumab-yhdp regimen led to a significantly shorter time to platelet count response versus plasma exchange and immunosuppression alone.

In the multicenter, double-blind, placebo-controlled HERCULES trial, 145 patients experiencing an aTTP episode were randomized to receive caplacizumab-yhdp at 10-mg intravenous loading bolus followed by 10 mg daily subcutaneously combined with plasma exchange and immunosuppressive therapy or placebo with the 2 standard therapies.

Results showed that the median time to normalization of the platelet count was shorter with caplacizumab-yhdp at 2.68 days versus placebo at 2.88 days. Additionally, caplacizumab-yhdp demonstrated a significant reduction on a composite endpoint of aTTP-related death, recurrence of aTTP, or a major thromboembolic event during treatment versus plasma exchange and immunosuppression alone. There was also a lower percentage of aTTP recurrences in the overall study period compared with plasma exchange and immunosuppression alone.


The FDA has granted a priority review designation to a supplemental biologics license application for the combination of avelumab and axitinib as a treatment for patients with advanced renal cell carcinoma.

The decision is based on findings from the phase III JAVELIN Renal 101 trial, which showed that the combination significantly improved progression-free survival and doubled the objective response rates versus sunitinib in patients with treatment-naïve advanced RCC, regardless of PD-L1 expression.

In the PD-L1—positive population, findings showed that the median PFS was 13.8 months with avelumab/axitinib compared with 7.2 months with sunitinib, leading to a 39% reduction in the risk of disease progression or death. Moreover, the ORR with the combination was 55.2%, which included 4 complete responses and 51 partial responses; the ORR with sunitinib was 25.5%. Twenty-seven patients in the combination arm had stable disease and 11 had progressive disease.

In the overall population, the median PFS with the combination of avelumab and axitinib versus sunitinib was 13.8 months and 8.4 months, respectively. Additionally, the ORR with avelumab/axitinib was 51.4% and 25.7% with sunitinib. In the combination arm, the ORR included 3 CRs and 48 PRs; 30 patients had SD and 12 patients had PD.

The FDA is expected to decide on the application in June 2019.


In head and neck squamous cell carcinoma, the FDA granted a priority review designation to a supplemental biologics license application for pembrolizumab alone or in combination with platinum and 5-fluorouracil chemotherapy as a frontline therapy for patients with recurrent or metastatic disease.

The sBLA is based on results from the phase III KEYNOTE-048 trial, in which single-agent pembrolizumab significantly improved overall survival versus standard chemotherapy in patients whose tumors expressed PD-L1 with a combined positive score at least 20 and CPS at least 1. An OS improvement was also observed with pembrolizumab plus chemotherapy in the overall population.

Moreover, the objective response rates were 23.3% and 36.1% with pembrolizumab and standard therapy, respectively; however, the median DOR was longer with the PD-1 inhibitor at 20.9 months versus 4.5 months.

Under the Prescription Drug User Fee Act, the FDA will decide on the sBLA by June 10, 2019.

Additionally, KEYNOTE-048 is the confirmatory trial for the phase Ib KEYNOTE-012 trial, which was the basis for the accelerated approval in August 2016 for single-agent pembrolizumab for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.


The FDA has scheduled an Oncologic Drugs Advisory Committee hearing for February 26, 2019, to discuss a new drug application for selinexor in combination with dexamethasone for the treatment of patients with penta-refractory multiple myeloma.

The NDA was submitted for an accelerated approval for patients who have received at least 3 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-targeted antibody, and to their most recent treatment. The agency granted a priority review designation to the NDA in October 2018.

Under the Prescription Drug User Fee Date, the FDA must make a decision on the approval by April 6, 2019. Karyopharm, the developer of selinexor, also submitted a marketing authorization application to the European Medicines Agency for conditional approval for the same indication.

The application is based on findings from the multicenter phase IIb STORM study, which demonstrated that the combination of selinexor and dexamethasone elicited a 26.2% overall response rate and an 8.6-month median overall survival.


In graft-versus-host disease, the FDA has added 3 months to the review period for a supplemental new drug application for ruxolitinib for the treatment of patients with acute disease who have had an inadequate response to corticosteroids. This makes the new action date May 24, 2019.

The extension will allow ample time for the FDA to review additional data the agency requested from Incyte, the manufacturer of the JAK1/JAK2 inhibitor ruxolitinib. The sNDA, which previously received a priority review, is based on results from the pivotal phase II REACH1 trial. Here, ruxolitinib combined with corticosteroids induced an overall response rate of 55% at day 28 in patients with steroid-refractory aGVHD, which met the primary endpoint of the study.

Additionally, 52 patients had a response at any time point in the study, translating to a best ORR of 73%.

The FDA granted a breakthrough therapy designation to ruxolitinib in June 2016 for the treatment of patients with aGVHD.


This week, we sat down with Dr Scott Kopetz, of the The University of Texas MD Anderson Cancer Center, discusses combining BRAF, MEK, and EGFR inhibition in metastatic colorectal cancer.

That’s all for today.

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