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FDA Approvals in ALL and Breast Cancer, Priority Review Designations in CML and Follicular Lymphoma, and More

Gina Columbus
Published Online: Friday, Sep 01, 2017



Today-

FDA approvals in acute lymphoblastic leukemia and breast cancer, priority review designations in chronic myeloid leukemia and follicular lymphoma, a breakthrough designation in breast cancer, a resubmission for a new drug application in neuroendocrine tumors, a European approval in kidney cancer, and an acquisition by Gilead Sciences.

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

The FDA has issued a historic approval of the first chimeric antigen receptor T-cell therapy, authorizing the use of tisagenlecleucel for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.

The approval of the immunocellular therapy follows the advice of the FDA’s Oncologic Drugs Advisory Committee, which voted 10-0 in July to recommend approval of tisagenlecleucel for pediatric ALL.

The primary efficacy analysis was based on phase II results from the single-arm, international ELIANA trial of 63 patients who received a single dose of tisagenlecleucel. Results showed that the overall remission rate was 82.5% in treated subjects. Forty patients had complete remission and 12 had complete remission with incomplete hematologic recovery.

In a separate action, the FDA has also expanded the approval of tocilizumab for the treatment of CAR T-cell–induced severe or life-threatening cytokine release syndrome in patients 2 years of age or older. 

*****************************************

In breast cancer, the FDA approved fulvestrant for use in hormone receptor-positive, HER2-negative locally-advanced or metastatic disease in postmenopausal women not previously treated with endocrine therapy.

The decision is based on data from the phase III FALCON trial, which demonstrated that fulvestrant extended median progression-free survival by 2.8 months versus the aromatase inhibitor anastrozole.

For postmenopausal women with HR-positive advanced or metastatic breast cancer, the recommended first-line treatment includes endocrine therapy with an aromatase inhibitor or tamoxifen.

**************************************

The FDA has granted a priority review designation to a supplemental new drug application for bosutinib for the frontline treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Additionally, the European Medicines Agency is also reviewing an application to use bosutinib for the same indication.

The FDA and EMA applications are based on findings from the multicenter, multinational, open-label, phase III BFORE trial, in which bosutinib was associated with a significantly higher rate of major molecular response at 12 months compared with imatinib in patients with newly diagnosed Ph+ CML.

The complete cytogenetic response by 12 months and cumulative incidence of CCyR was also statistically significant in favor of bosutinib.

*************************************

In follicular lymphoma, a supplemental biologics license application for obinutuzumab in combination with chemotherapy, followed by obinutuzumab alone, has been granted a priority review designation. The indication would be as a first-line treatment.

The sBLA stems from findings of the international phase III GALLIUM trial, in which the combination of obinutuzumab and chemotherapy in the first-line setting reduced the risk of disease progression or death by 32% versus rituximab plus chemotherapy.

Under the Prescription Drug Use Fee Act, the FDA is scheduled to make a decision on the approval on or before December 23, 2017.

At a median follow-up of 41.1 months, the hazard ratio for progression-free survival by investigator assessment was 0.68. Per independent review, the HR for PFS was 0.72. The median PFS had not been reached yet in either treatment arm.

*****************************************

DS-8201 has received an FDA breakthrough therapy designation for the treatment of patients with HER2-positive, locally advanced, or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine.

The investigational HER2-targeting antibody-drug conjugate is being explored in an ongoing, dose escalation/expansion phase I study, preliminary data from which are the basis for the FDA’s decision. In part 1 of the study, patients with breast, gastric, colorectal, salivary, and non–small cell lung cancer were included to determine an expansion cohort, which were then used in part 2 of the study.

The overall response rate in patients with breast cancer receiving the part 2 doses was 42.2% and the disease control rate was 97.8%. Among patients who previously received T-DM1, the ORR was 45.7% and the disease control rate was 100%. In those with prior T-DM1 plus pertuzumab, the corresponding rates were 46.7% and 100%, respectively.

Currently, the safety and efficacy of DS-8201 is being explored in the pivotal phase II DESTINY-Breast01 study in patients with HER2-positive, unresectable, and/or metastatic breast cancer that is resistant or refractory to T-DM1.

********************************

The FDA has accepted a resubmitted new drug application for Lutathera as a treatment for patients with gastroenteropancreatic neuroendocrine tumors. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final approval decision on or before January 26, 2018.

The NDA is based on the phase III NETTER-1 trial, which compared Lutathera with high-dose octreotide LAR for patients with grade 1 or 2 metastatic midgut NETs. In this study, Lutathera was associated with a 79% reduction in the risk of progression or death with versus octreotide. 

The FDA had granted a priority review designation to the NDA for Lutathera in June 2016, and was originally scheduled to make its final decision by December 28, 2016. However, on December 21, Advanced Accelerator Applications, the manufacturer of Lutathera, reported that the FDA had issued a complete response letter informing the company that the NDA would need to be resubmitted.

The complete response letter, which followed a discipline review letter issued in November 2016, requested new subgroup data, a safety update, and that revisions be made to the previously submitted data. The letter did not request the initiation of additional studies of Lutathera.

********************************

In renal cell carcinoma, the European Commission has approved tivozanib as a frontline treatment for patients with advanced disease. The drug is also indicated for patients who are VEGFR- and mTOR-inhibitor naïve following disease progression after 1 prior treatment with cytokine therapy.

The approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, which was based on the phase III TiVO-1 trial. Here, tivozanib was found to reduce the risk of disease progression or death by more than 20% versus sorafenib in patients with advanced RCC who received up to 1 prior line of therapy.

In the United States, the FDA rejected tivozanib in June 2013 after concluding the TiVO-1 findings showed inconsistent PFS and OS results. Furthermore, the agency found the risk-benefit assessment inconclusive after the FDA’s Oncologic Drugs Advisory Committee voted 13-1 against tivozanib.

********************************

Finally, Gilead announced its plans to acquire Kite Pharma, the developer of the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, also known as axi-cel. The acquisition will be made for $180.00 per share in cash, totaling approximately $11.9 billion. The decision was unanimously approved by both companies and is expected to complete later this year.

The FDA is currently considering a biologics license application for axi-cel for transplant-ineligible patients with relapsed or refractory non-Hodgkin lymphoma, which is based on data from the phase II ZUMA-1 study.

In addition to axi-cel, Kite has other CAR T-cell and T-cell receptor therapies in development that will be added to the oncology pipeline held by Gilead, which includes the approved PI3K inhibitor idelalisib. Additionally, Gilead has a phase III study underway for the MMP3 inhibitor andecaliximab for patients with gastric cancer.

********************************

This week, we sat down with Lewis C. Cantley, PhD, of Weill Cornell Medical College about being recognized as a 2017 Giant of Cancer Care in Scientific Advances.

That’s all for today.

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

FDA approvals in acute lymphoblastic leukemia and breast cancer, priority review designations in chronic myeloid leukemia and follicular lymphoma, a breakthrough designation in breast cancer, a resubmission for a new drug application in neuroendocrine tumors, a European approval in kidney cancer, and an acquisition by Gilead Sciences.

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

The FDA has issued a historic approval of the first chimeric antigen receptor T-cell therapy, authorizing the use of tisagenlecleucel for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse.

The approval of the immunocellular therapy follows the advice of the FDA’s Oncologic Drugs Advisory Committee, which voted 10-0 in July to recommend approval of tisagenlecleucel for pediatric ALL.

The primary efficacy analysis was based on phase II results from the single-arm, international ELIANA trial of 63 patients who received a single dose of tisagenlecleucel. Results showed that the overall remission rate was 82.5% in treated subjects. Forty patients had complete remission and 12 had complete remission with incomplete hematologic recovery.

In a separate action, the FDA has also expanded the approval of tocilizumab for the treatment of CAR T-cell–induced severe or life-threatening cytokine release syndrome in patients 2 years of age or older. 

*****************************************

In breast cancer, the FDA approved fulvestrant for use in hormone receptor-positive, HER2-negative locally-advanced or metastatic disease in postmenopausal women not previously treated with endocrine therapy.

The decision is based on data from the phase III FALCON trial, which demonstrated that fulvestrant extended median progression-free survival by 2.8 months versus the aromatase inhibitor anastrozole.

For postmenopausal women with HR-positive advanced or metastatic breast cancer, the recommended first-line treatment includes endocrine therapy with an aromatase inhibitor or tamoxifen.

**************************************

The FDA has granted a priority review designation to a supplemental new drug application for bosutinib for the frontline treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia.

Additionally, the European Medicines Agency is also reviewing an application to use bosutinib for the same indication.

The FDA and EMA applications are based on findings from the multicenter, multinational, open-label, phase III BFORE trial, in which bosutinib was associated with a significantly higher rate of major molecular response at 12 months compared with imatinib in patients with newly diagnosed Ph+ CML.

The complete cytogenetic response by 12 months and cumulative incidence of CCyR was also statistically significant in favor of bosutinib.

*************************************

In follicular lymphoma, a supplemental biologics license application for obinutuzumab in combination with chemotherapy, followed by obinutuzumab alone, has been granted a priority review designation. The indication would be as a first-line treatment.

The sBLA stems from findings of the international phase III GALLIUM trial, in which the combination of obinutuzumab and chemotherapy in the first-line setting reduced the risk of disease progression or death by 32% versus rituximab plus chemotherapy.

Under the Prescription Drug Use Fee Act, the FDA is scheduled to make a decision on the approval on or before December 23, 2017.

At a median follow-up of 41.1 months, the hazard ratio for progression-free survival by investigator assessment was 0.68. Per independent review, the HR for PFS was 0.72. The median PFS had not been reached yet in either treatment arm.

*****************************************

DS-8201 has received an FDA breakthrough therapy designation for the treatment of patients with HER2-positive, locally advanced, or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine.

The investigational HER2-targeting antibody-drug conjugate is being explored in an ongoing, dose escalation/expansion phase I study, preliminary data from which are the basis for the FDA’s decision. In part 1 of the study, patients with breast, gastric, colorectal, salivary, and non–small cell lung cancer were included to determine an expansion cohort, which were then used in part 2 of the study.

The overall response rate in patients with breast cancer receiving the part 2 doses was 42.2% and the disease control rate was 97.8%. Among patients who previously received T-DM1, the ORR was 45.7% and the disease control rate was 100%. In those with prior T-DM1 plus pertuzumab, the corresponding rates were 46.7% and 100%, respectively.

Currently, the safety and efficacy of DS-8201 is being explored in the pivotal phase II DESTINY-Breast01 study in patients with HER2-positive, unresectable, and/or metastatic breast cancer that is resistant or refractory to T-DM1.

********************************

The FDA has accepted a resubmitted new drug application for Lutathera as a treatment for patients with gastroenteropancreatic neuroendocrine tumors. Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final approval decision on or before January 26, 2018.

The NDA is based on the phase III NETTER-1 trial, which compared Lutathera with high-dose octreotide LAR for patients with grade 1 or 2 metastatic midgut NETs. In this study, Lutathera was associated with a 79% reduction in the risk of progression or death with versus octreotide. 

The FDA had granted a priority review designation to the NDA for Lutathera in June 2016, and was originally scheduled to make its final decision by December 28, 2016. However, on December 21, Advanced Accelerator Applications, the manufacturer of Lutathera, reported that the FDA had issued a complete response letter informing the company that the NDA would need to be resubmitted.

The complete response letter, which followed a discipline review letter issued in November 2016, requested new subgroup data, a safety update, and that revisions be made to the previously submitted data. The letter did not request the initiation of additional studies of Lutathera.

********************************

In renal cell carcinoma, the European Commission has approved tivozanib as a frontline treatment for patients with advanced disease. The drug is also indicated for patients who are VEGFR- and mTOR-inhibitor naïve following disease progression after 1 prior treatment with cytokine therapy.

The approval follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use, which was based on the phase III TiVO-1 trial. Here, tivozanib was found to reduce the risk of disease progression or death by more than 20% versus sorafenib in patients with advanced RCC who received up to 1 prior line of therapy.

In the United States, the FDA rejected tivozanib in June 2013 after concluding the TiVO-1 findings showed inconsistent PFS and OS results. Furthermore, the agency found the risk-benefit assessment inconclusive after the FDA’s Oncologic Drugs Advisory Committee voted 13-1 against tivozanib.

********************************

Finally, Gilead announced its plans to acquire Kite Pharma, the developer of the chimeric antigen receptor T-cell therapy axicabtagene ciloleucel, also known as axi-cel. The acquisition will be made for $180.00 per share in cash, totaling approximately $11.9 billion. The decision was unanimously approved by both companies and is expected to complete later this year.

The FDA is currently considering a biologics license application for axi-cel for transplant-ineligible patients with relapsed or refractory non-Hodgkin lymphoma, which is based on data from the phase II ZUMA-1 study.

In addition to axi-cel, Kite has other CAR T-cell and T-cell receptor therapies in development that will be added to the oncology pipeline held by Gilead, which includes the approved PI3K inhibitor idelalisib. Additionally, Gilead has a phase III study underway for the MMP3 inhibitor andecaliximab for patients with gastric cancer.

********************************

This week, we sat down with Lewis C. Cantley, PhD, of Weill Cornell Medical College about being recognized as a 2017 Giant of Cancer Care in Scientific Advances.

That’s all for today.

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