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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, December 1, 2016

​The FDA has granted Fast Track designation to the investigational HER2-targeting antibody drug conjugate DS-8201 for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including ado-trastuzumab emtansine (T-DM1).

Fast Track designation was granted based on results from the dose escalation part of a two-part phase I study that assessed the safety, tolerability and preliminary efficacy of DS-8201. The second part (dose expansion) of the ongoing phase I study is enrolling patients in Japan and the U.S. to evaluate the safety and efficacy of DS-8201 in four different cohorts of HER2 expressing cancers: patients with HER2+ metastatic breast cancer previously treated with T-DM1; patients with HER2+ gastric or gastroesophageal junction adenocarcinoma previously treated with trastuzumab; patients with HER2 low expressing breast cancer; and patients with other solid cancers that express HER2.

Tuesday, November 29, 2016

The FDA has granted ponatinib (Iclusig) full approval for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated; and for the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I positive Ph+ ALL.

This full approval and label update is based on 48-month follow-up data (as of August 2015) from the pivotal phase II PACE clinical trial of ponatinib in heavily pretreated patients with resistant or intolerant CML or Ph+ ALL.

"The longer follow up of the PACE study confirms the clinical benefit of ponatinib in this setting. We had learned from the initial report of the high response rate with ponatinib among CML patients with resistance or intolerance to prior therapies. The 4-year follow-up and updated safety profile demonstrate durability of responses in this heavily pre-treated population. These results solidify ponatinib as an important and valuable treatment option for refractory patients with CML where no other TKI therapy is appropriate, including those who have the T315I mutation," stated Jorge Cortes, MD, Professor and Deputy Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, and a leading investigator in the PACE trial.

Four-Year PACE Trial Data Included in Labeling Update

The efficacy and safety of ponatinib in CML and Ph+ ALL patients resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation, were evaluated in the PACE trial. A total of 449 patients were treated with ponatinib at a starting dose of 45 mg/day.

An estimated 93 percent of patients previously received two or more approved TKIs, and 56 percent of all patients had received three or more approved TKIs. Enrollment in the PACE trial was completed in October 2011. Updated data on CP-CML patients (n=270) from the ongoing trial indicate that with a minimum follow-up of 48 months (data as of August 3, 2015), 110 patients continued to receive ponatinib. Additional data for CP-CML patients include:

  • Fifty-five percent of CP-CML patients achieved major cytogenetic response (MCyR) (primary endpoint) at any time. The median duration of MCyR (range 2.7 months to 50+ months) has not been reached.
  • Thirty-nine percent of patients achieved a major molecular response (MMR) at any time. The median duration of MMR (range 1.7 months to 50+ months) has not been reached.
  • With 4 years of follow-up, 33 percent (150/449) of all patients experienced arterial occlusive events (AOE). Twenty-one percent of patients experienced cardiac vascular, 12 percent experienced peripheral vascular, and 9 percent experienced cerebrovascular arterial occlusive events, with some patients experiencing more than one type of AOE. Twenty-two percent experienced arterial occlusive serious adverse reactions (12% cardiac vascular, 8% peripheral vascular, and 7% cerebrovascular).
  • Six percent of all patients experienced a venous thromboembolic event.
  • The most common any-grade treatment-emergent adverse events occurring in ≥ 20 percent of CP-CML patients included hypertension (69%), rash (63%), abdominal pain (48%), fatigue (47%), headache (43%), arterial ischemia (42%), dry skin (42%), constipation (41%), arthralgia (32%), nausea (28%), pyrexia (26%), peripheral neuropathy (24%), myalgia (24%), pain in extremity (23%), back pain (21%), diarrhea (20%). Post-marketing cases of reversible posterior leukoencephalopathy syndrome have been reported. ​

OPTIC Post-Marketing Trial

Patients are currently being enrolled in the OPTIC post-marketing trial of ponatinib, which is expected to inform the optimal dosing of Iclusig.

This randomized, dose-ranging trial is enrolling patients with CP-CML who are resistant to at least two approved TKIs. Patients are randomized equally to receive once-daily administration of 45 mg (cohort A), 30 mg (cohort B) or 15 mg (cohort C) of ponatinib.

Patients in cohorts A and B will have their daily dose reduced to 15 mg upon achievement of MCyR. The primary endpoint of the trial is MCyR by 12 months for each cohort. Initial data from the OPTIC trial to expected to be submitted to the American Society of Hematology (ASH) meeting in 2017. 

Monday, November 28, 2016

The FDA recently accepted for review the supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda), an anti-PD-1 therapy, for the treatment of previously treated patients with advanced microsatellite instability-high (MSI-H) cancer.

The FDA granted Priority Review with a PDUFA, or target action date, of March 8, 2017; the sBLA will be reviewed under the FDA's Accelerated Approval program based on tumor response rate and durability of response. The FDA recently granted Breakthrough Therapy Designation to pembrolizumab for unresectable or metastatic MSI-H non-colorectal cancer, and previously granted it for the treatment of patients with unresectable or metastatic MSI-H colorectal cancer.

The application, which is seeking approval for pembrolizumab at a fixed dose of 200 mg every 3 weeks, is based on data from five uncontrolled, open-label, multi-cohort, multi-site phase I/II trials investigating the activity of pembrolizumab in MSI-H cancer.

Thursday, November 10, 2016

The FDA approved atezolizumab (Tecentriq) for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on a targeted therapy if their tumor has EGFR or ALK gene abnormalities.

This approval is based on results from the randomized phase III OAK and phase II POPLAR studies. The largest study, OAK, showed that atezolizumab helped people in the study live a median of 13.8 months,

4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR=0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.

The atezolizumab development program includes more than 15 clinical trials in lung cancer, including seven phase III studies in previously untreated lung cancer. These studies are evaluating the use of atezolizumab alone or in combination with other medicines.

Thursday, November 10, 2016

The FDA has granted Breakthrough Therapy Designation for the anaplastic lymphoma kinase (ALK) inhibitor alectinib (Alecensa) for the treatment of adult patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.

The FDA's Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and help ensure patients have access to them through FDA approval as soon as possible. Alectinib received its first designation in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.

Alectinib was granted accelerated approval by the FDA in December 2015 for the treatment of people with ALK-positive NSCLC who have progressed on or are intolerant to crizotinib. ALEX, a global, randomized phase III study, is ongoing, comparing alectinib to crizotinib as a first-line treatment for people with advanced NSCLC whose tumors were characterized as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry test.

About the Author

Sarah DiGiulio