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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Thursday, March 21, 2019

The FDA recently approved atezolizumab, in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).

This approval is based on results from the phase III IMpower133 study, which showed that atezolizumab in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS]=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the intention-to-treat (ITT) population.

The atezolizumab-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017). Safety for the atezolizumab and chemotherapy combination appeared consistent with the known safety profile of atezolizumab.

Atezolizumab is a monoclonal antibody designed to bind with the protein PD-L1. It is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the re-activation of T cells. Atezolizumab may also affect normal cells.
"Extensive-stage small cell lung cancer is a highly aggressive form of lung cancer, which until now, has seen limited treatment advances over the last 20 years," said Andrea Ferris, President and CEO of LUNGevity Foundation. "[This] approval of atezolizumab is an important step forward in ensuring that people across the spectrum of lung cancer types have effective new therapies."

IMpower133 is a phase III, multicenter, double-blinded, randomized placebo-controlled study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and etoposide versus carboplatin and etoposide alone in chemotherapy-naïve adults with ES-SCLC. The study enrolled 403 people who were randomized equally (1:1) to receive:

  • Atezolizumab in combination with carboplatin and etoposide (Arm A), or
  • Placebo in combination with carboplatin and etoposide (Arm B, control arm).

During the treatment-induction phase, people received treatment on 21-day cycles for 4 cycles, followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were PFS as determined by the investigator using RECIST v1.1 and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below:

  • Atezolizumab in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the ITT population.
  • The atezolizumab-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017).
  • Safety for the atezolizumab and chemotherapy combination appeared consistent with the known safety profile of atezolizumab. Serious adverse reactions occurred in 37 percent of people receiving atezolizumab plus chemotherapy compared with 35 percent of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving atezolizumab plus chemotherapy were fatigue/asthenia (39%), nausea (38%), alopecia (37%), decreased appetite (27%), constipation (26%), and vomiting (20%).

Results from the study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.

Atezolizumab is also approved in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. Additionally, atezolizumab is approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab.

Monday, March 11, 2019

The FDA has granted Priority Review designation for the supplemental New Drug Application (sNDA) for lenalidomide in combination with rituximab (R²) for the treatment of patients with previously treated follicular and marginal zone lymphoma. Under the Prescription Drug User Fee Act, the FDA has set its action date as June 27, 2019.

The sNDA is based on results from the randomized, double-blind, phase III AUGMENT study, which evaluated the efficacy and safety of the investigational R² combination versus rituximab plus placebo in patients with relapsed/refractory follicular and marginal zone lymphoma. Results from the study were presented at the 2018 American Society of Hematology Annual Meeting.

AUGMENT is a phase III, randomized, double-blind clinical trial evaluating the efficacy and safety of lenalidomide in combination with rituximab (R²) versus rituximab plus placebo in patients with relapsed/refractory follicular and marginal zone lymphoma.

The primary endpoint was progression-free survival, defined as the time from date of randomization to the first observation of disease progression or death due to any cause. Secondary endpoints included overall response rate, durable complete response rate, complete response rate, duration of response, duration of complete response, overall survival, event-free survival, and time to next anti-lymphoma therapy.

Monday, February 25, 2019

The FDA has granted Orphan Drug Designation (ODD) to etoposide toniribate for the treatment of relapsed/refractory biliary tract cancer, also known as cholangiocarcinoma.

Biliary tract cancer is a rare tumour with approximately 8,000 patients diagnosed in the U.S. every year and 10,571 in Europe. The FDA grants ODD status to medicines intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. Radical surgery is the only curative treatment for biliary tract cancer but, in most cases, the cancer is inoperable. Patients who fail first-line chemotherapy have limited treatment options and the standard of care is generally palliative. The 5-year survival rates for patients with biliary tract cancer are very low, approximately 15 percent.

Etoposide toniribate has shown encouraging data in phase II trials and this data has been key in securing the ODD. This news is in addition to the European Medicines Agency (EMA) also granting orphan designation on June 4, 2014. As with the FDA, this designation allows protocol assistance, reduced fees and 10-years marketing exclusivity in that disease after approval. It can also lead to speedier reimbursement in many EU member states.

Etoposide toniribate is to be accelerated through a phase III trial, with the aim of providing a potential additional treatment option in this area of unmet patient need.

Monday, February 25, 2019

The FDA has approved trifluridine/tipiracil as a treatment for adult patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

The approval follows an FDA Priority Review designation and is based on data from a global, randomized, phase III TAGS trial evaluating trifluridine/tipiracil plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated advanced gastric cancer or GEJ adenocarcinoma following progression or intolerance to previous lines of standard therapy.

The trial met its primary and secondary endpoints demonstrating prolonged overall survival (OS) with trifluridine/tipiracil versus placebo, and a safety profile consistent with prior experience with this drug. Full results from the TAGS trial were presented at the European Society of Medical Oncology (ESMO) 2018 Congress with a simultaneous publication in The Lancet Oncology (2018;19(11):1437-1438).

This approval expands the current indication for trifluridine/tipiracil in the U.S., where it is currently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with standard chemotherapy, based on results obtained in the RECOURSE trial.

TAGS (TAS-102 Gastric Study) is a global, randomized, double-blind phase III study evaluating trifluridine/tipiracil (TAS-102) plus BSC versus placebo plus BSC in patients with metastatic gastric or GEJ cancer, refractory to standard treatments. The primary endpoint in the TAGS trial was OS, and the main secondary endpoint measures included progression-free survival (PFS), safety and tolerability, as well as quality of life. The study enrolled 507 adult patients with metastatic gastric or GEJ cancer who had previously received at least two prior regimens for advanced disease and was conducted in 17 countries and 110 sites around the world.

Wednesday, February 13, 2019

The European Commission (EC) extended the current marketing authorization of brentuximab vedotin to include treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine, and dacarbazine). Brentuximab vedotin is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on December 13, 2018.

"The decision by the European Commission is a welcomed advancement for patients with previously untreated stage IV Hodgkin lymphoma—a population that has not been offered a new treatment option in decades," said Anna Sureda, MD, PhD, Head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d'Oncologia–Hospital Duran i Reynals. "Patients with stage IV disease carry a higher risk of progression following their first therapy and experience poorer outcomes as a result. The approval of this regimen may help address this unmet need by providing European physicians and their patients with a new option that showed significant benefit compared to ABVD along with a safety profile consistent with when brentuximab vedotin is used as a single agent."

The approval is based on the results of the randomized, open-label, two-arm, multi-center phase III ECHELON-1 study designed to compare brentuximab vedotin plus AVD to ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) as a therapy in adult patients with previously untreated Hodgkin lymphoma.

The trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm (HR 0.77; p-value=0.035), which corresponds to a 23 percent reduction in the risk of progression, death, or need for additional anticancer therapy. Key subgroup analyses showed a larger effect in patients with stage IV Hodgkin lymphoma in the brentuximab vedotin plus AVD arm versus the control arm (modified PFS; HR 0.71; p-value = 0.023).

The safety profile of brentuximab vedotin plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen. The most common clinically relevant adverse events of any grade that occurred in at least 15 percent of patients in the brentuximab vedotin plus AVD and ABVD arms were: neutropenia, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhea, pyrexia, peripheral neuropathy, abdominal pain, and stomatitis. In both the brentuximab vedotin plus AVD and ABVD arms, the most common grade 3 or 4 events were neutropenia, febrile neutropenia, and neutrophil count decrease.

This decision by the European Commission means that brentuximab vedotin in combination with AVD is now approved for marketing of this indication in the 28 member states of the European Union and applicable in Norway, Liechtenstein, and Iceland.