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FDA Approvals in NTRK-Fusion Cancers, AML, and SAA, and Priority Review in AML

Gina Columbus
Published: Friday, Nov 30, 2018



Today-

An FDA approval in NTRK-fusion cancers, acute myeloid leukemia, and severe aplastic anemia, and a priority review designation in acute myeloid leukemia.

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

The FDA has granted an accelerated approval to larotrectinib, known by the trade name Vitrakvi, for the treatment of adult and pediatric patients with solid tumors that harbor an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following therapy.

The decision is based on findings from patients with TRK-positive tumors who were enrolled across 3 clinical trials: phase I adult LOXO-TRK-14001 trial, the phase II NAVIGATE trial, and the phase I/II SCOUT pediatric trial. In data that were published in the New England Journal of Medicine in February 2018, larotrectinib was associated with an objective response rate of 75% by independent review and 80% by investigator assessment in 55 evaluable patients. In the independent assessment, there were 7 complete responses, 34 partial responses, and 7 patients with stable disease.

At 1 year of follow-up, 71% of responses were ongoing, and 55% of patients remained progression-free at 1 year. The median duration of response had not been reached after a median follow-up of 8.3 months, which was also true for median progression-free survival after a median follow-up of 9.9 months.

The accelerated approval of larotrectinib in this setting is contingent on the results of a confirmatory trial.

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The FDA has granted an accelerated approval to venetoclax for use in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of adult patients with newly diagnosed acute myeloid leukemia. The indication is specific to those who are aged 75 years or older, or have comorbidities that preclude use of intensive induction chemotherapy.

The accelerated approval is contingent on the results of a confirmatory trial.

The decision is based on 2 phase Ib/II trials in this setting, which were the M14-358 study and the M14-387 study. In M14-358, the combination of venetoclax and azacitidine led to a complete remission rate of 37% and a CR with partial hematological recovery rate of 24%. The rates were 54% and 7.7%, respectively, with the combination of venetoclax and decitabine.

M14-387 examined venetoclax in combination with low-dose cytarabine, which led to 21% CR and CRh rates with the combination.

Moreover, the median time to first CR or CRh was 1.0 month in the azacitidine group and 1.9 months for the decitabine group. Five of the 67 patients treated with venetoclax/azacitidine went on to receive stem cell transplant.

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Also in acute myeloid leukemia, the FDA approved glasdegib, known by the trade name Daurismo, for use in combination with low-dose cytarabine for the treatment of patients with newly diagnosed disease who are aged 75 years or older or who are ineligible for intensive chemotherapy.

The approval was based on the phase II BRIGHT 1003 trial, in which 115 patients with newly diagnosed AML were randomized in a 2:1 ratio to receive glasdegib plus LDAC or LDAC alone. Results showed that the addition of glasdegib to LDAC reduced the risk of death by 54% compared with LDAC alone. Additionally, the median overall survival was 8.3 months versus 4.3 months, respectively, and the complete response rate was 18.2% with the glasdegib combination compared with 2.6% with LDAC alone.

Seventy-nine percent of patients in the glasdegib arm experienced serious adverse events. Such events that occurred in more than 5% of patients treated with glasdegib plus LDAC included febrile neutropenia, pneumonia, hemorrhage, anemia, and sepsis. The FDA label for glasdegib includes a boxed warning for embryo-fetal toxicity.

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The FDA has expanded the approval of eltrombopag in combination with standard immunosuppressive therapy to include newly diagnosed adult and pediatric patients 2 years and older with severe aplastic anemia. The agency also granted the agent a breakthrough therapy designation as a counter measure for hematopoietic sub-syndrome of acute radiation syndrome.

The decision is based on a Novartis analysis sponsored by the National Heart, Lung, and Blood Institute Division of Intramural Research Program and conducted under a Cooperative Research and Development Agreement. Results showed that treatment with eltrombopag given concurrently with standard IST led to an overall response rate at 6 months of 79%.

Moreover, 44% of definitive IST-naïve patients achieved a complete response at 6 months when treated with concurrent eltrombopag; this was 27% higher than the historically observed CR rate with standard IST alone.

Eltrombopag is an oral thrombopoietin receptor agonist with a prior indication for patients with SAA who have had an insufficient response to standard therapy, for adults and pediatric patients with chronic immune thrombocytopenia who are refractory to other therapies, and for the treatment of thrombocytopenia in patients with chronic hepatitis C virus infection.

Additional updated data showed that the median duration of response was 24.3 months for patients treated with eltrombopag for 6 months in combination with horse anti-thymocyte globulin and cyclosporine followed by maintenance CsA4.

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

In acute myeloid leukemia, the FDA granted a priority review designation to a new drug application for quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive disease.

The designation is based on findings from the phase III QuANTUM-R study, results of which showed that quizartinib reduced the risk of death by 24% compared with salvage chemotherapy in patients with FLT3-ITD–positive relapsed/refractory AML after first-line treatment with or without hematopoietic stem cell transplantation.

At a median follow-up of 23.5 months, the median overall survival was 6.2 months with quizartinib versus 4.7 months with salvage chemotherapy. Updated results are scheduled to be presented at the 2018 ASH Annual Meeting.

Under the Prescription Drug User Fee Act, the FDA will decide on the application by May 25, 2019.

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This week, we sat down with Dr Ajai Chari, of Mount Sinai Health System, to discuss the evolution of therapy for patients with multiple myeloma.

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

And this weekend, stay tuned for our News Network: On Location broadcast at the 2018 ASH Annual Meeting in San Diego, California! We’ll be recapping the top news presented each day during the meeting and interviewing key opinion leaders for their insight on some of the pivotal abstracts. To register for a reminder when the broadcast goes live, visit onclive.com/live.

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That’s all for today.

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

An FDA approval in NTRK-fusion cancers, acute myeloid leukemia, and severe aplastic anemia, and a priority review designation in acute myeloid leukemia.

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

The FDA has granted an accelerated approval to larotrectinib, known by the trade name Vitrakvi, for the treatment of adult and pediatric patients with solid tumors that harbor an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following therapy.

The decision is based on findings from patients with TRK-positive tumors who were enrolled across 3 clinical trials: phase I adult LOXO-TRK-14001 trial, the phase II NAVIGATE trial, and the phase I/II SCOUT pediatric trial. In data that were published in the New England Journal of Medicine in February 2018, larotrectinib was associated with an objective response rate of 75% by independent review and 80% by investigator assessment in 55 evaluable patients. In the independent assessment, there were 7 complete responses, 34 partial responses, and 7 patients with stable disease.

At 1 year of follow-up, 71% of responses were ongoing, and 55% of patients remained progression-free at 1 year. The median duration of response had not been reached after a median follow-up of 8.3 months, which was also true for median progression-free survival after a median follow-up of 9.9 months.

The accelerated approval of larotrectinib in this setting is contingent on the results of a confirmatory trial.

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

The FDA has granted an accelerated approval to venetoclax for use in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of adult patients with newly diagnosed acute myeloid leukemia. The indication is specific to those who are aged 75 years or older, or have comorbidities that preclude use of intensive induction chemotherapy.

The accelerated approval is contingent on the results of a confirmatory trial.

The decision is based on 2 phase Ib/II trials in this setting, which were the M14-358 study and the M14-387 study. In M14-358, the combination of venetoclax and azacitidine led to a complete remission rate of 37% and a CR with partial hematological recovery rate of 24%. The rates were 54% and 7.7%, respectively, with the combination of venetoclax and decitabine.

M14-387 examined venetoclax in combination with low-dose cytarabine, which led to 21% CR and CRh rates with the combination.

Moreover, the median time to first CR or CRh was 1.0 month in the azacitidine group and 1.9 months for the decitabine group. Five of the 67 patients treated with venetoclax/azacitidine went on to receive stem cell transplant.

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

Also in acute myeloid leukemia, the FDA approved glasdegib, known by the trade name Daurismo, for use in combination with low-dose cytarabine for the treatment of patients with newly diagnosed disease who are aged 75 years or older or who are ineligible for intensive chemotherapy.

The approval was based on the phase II BRIGHT 1003 trial, in which 115 patients with newly diagnosed AML were randomized in a 2:1 ratio to receive glasdegib plus LDAC or LDAC alone. Results showed that the addition of glasdegib to LDAC reduced the risk of death by 54% compared with LDAC alone. Additionally, the median overall survival was 8.3 months versus 4.3 months, respectively, and the complete response rate was 18.2% with the glasdegib combination compared with 2.6% with LDAC alone.

Seventy-nine percent of patients in the glasdegib arm experienced serious adverse events. Such events that occurred in more than 5% of patients treated with glasdegib plus LDAC included febrile neutropenia, pneumonia, hemorrhage, anemia, and sepsis. The FDA label for glasdegib includes a boxed warning for embryo-fetal toxicity.

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

The FDA has expanded the approval of eltrombopag in combination with standard immunosuppressive therapy to include newly diagnosed adult and pediatric patients 2 years and older with severe aplastic anemia. The agency also granted the agent a breakthrough therapy designation as a counter measure for hematopoietic sub-syndrome of acute radiation syndrome.

The decision is based on a Novartis analysis sponsored by the National Heart, Lung, and Blood Institute Division of Intramural Research Program and conducted under a Cooperative Research and Development Agreement. Results showed that treatment with eltrombopag given concurrently with standard IST led to an overall response rate at 6 months of 79%.

Moreover, 44% of definitive IST-naïve patients achieved a complete response at 6 months when treated with concurrent eltrombopag; this was 27% higher than the historically observed CR rate with standard IST alone.

Eltrombopag is an oral thrombopoietin receptor agonist with a prior indication for patients with SAA who have had an insufficient response to standard therapy, for adults and pediatric patients with chronic immune thrombocytopenia who are refractory to other therapies, and for the treatment of thrombocytopenia in patients with chronic hepatitis C virus infection.

Additional updated data showed that the median duration of response was 24.3 months for patients treated with eltrombopag for 6 months in combination with horse anti-thymocyte globulin and cyclosporine followed by maintenance CsA4.

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

In acute myeloid leukemia, the FDA granted a priority review designation to a new drug application for quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD–positive disease.

The designation is based on findings from the phase III QuANTUM-R study, results of which showed that quizartinib reduced the risk of death by 24% compared with salvage chemotherapy in patients with FLT3-ITD–positive relapsed/refractory AML after first-line treatment with or without hematopoietic stem cell transplantation.

At a median follow-up of 23.5 months, the median overall survival was 6.2 months with quizartinib versus 4.7 months with salvage chemotherapy. Updated results are scheduled to be presented at the 2018 ASH Annual Meeting.

Under the Prescription Drug User Fee Act, the FDA will decide on the application by May 25, 2019.

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

This week, we sat down with Dr Ajai Chari, of Mount Sinai Health System, to discuss the evolution of therapy for patients with multiple myeloma.

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

And this weekend, stay tuned for our News Network: On Location broadcast at the 2018 ASH Annual Meeting in San Diego, California! We’ll be recapping the top news presented each day during the meeting and interviewing key opinion leaders for their insight on some of the pivotal abstracts. To register for a reminder when the broadcast goes live, visit onclive.com/live.

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

That’s all for today.

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