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FDA Approval in AML, NDA Submitted in Myeloma, Clinical Hold on CAR T-cell Therapy Trials, and More

Gina Columbus
Published Online: Friday, Sep 08, 2017



Today-

An FDA approval in acute myeloid leukemia, a new drug application submitted in multiple myeloma, encouraging results in a chronic lymphocytic leukemia trial, a delayed decision on a biosimilar, a clinical hold on CAR T-cell therapy trials, and a European approval in bladder cancer.

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

The FDA has approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia.

The antibody-drug conjugate was also approved for the treatment of patients aged 2 years and older with CD33-positive relapsed/refractory AML. The decision follows the recommendation of the FDA’s Oncologic Drugs Advisory Committee, which voted 6 to 1 recommending approval during a meeting this past July.  

The decision was based on data from a number of trials, including the ALFA-0701, AML-19, and MyloFrance-1.1 trials. In ALFA-0701, gemtuzumab ozogamicin was associated with a statistically significant improvement in event-free survival of 7.8 months. However, the drug was not associated with a significant improvement in overall survival.

In Study AML-19, the agent was associated with a reduction in the risk of death by 31%, as well as a median OS of 4.9 months versus 3.6 months in the control arm.

The label for gemtuzumab ozogamicin includes a boxed warning for hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome.

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In multiple myeloma, the FDA has accepted a supplemental new drug application seeking to add overall survival data from the phase III ENDEAVOR trial to the label for carfilzomib for use in patients with relapsed or refractory disease.

The primary OS analysis from ENDEAVOR showed that carfilzomib reduced the risk of death by 21% versus bortezomib. Moreover, carfilzomib plus dexamethasone was found to extend overall survival by 7.6 months versus bortezomib combined with dexamethasone.

Currently, carfilzomib is approved in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy. The treatment is also approved as a monotherapy for relapsed/refractory patients who have received 1 or more lines of therapy.

The Prescription Drug User Fee Act action date for the FDA’s decision on the label update is April 30, 2018.

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The PI3K-delta and –gamma inhibitor duvelisib was found to reduce the risk of disease progression or death by 48% versus ofatumumab in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who were enrolled in the phase III DUO trial.

Findings showed that, in the overall population, the median progression-free survival with duvelisib was 3.4 months longer compared with ofatumumab. In patients with a 17p deletion, the median PFS benefit was 3.7 months.

The median PFS was 13.3 months in the duvelisib arm compared with 9.9 months in the ofatumumab arm. In patients with a 17p deletion, the median PFS was 12.7 versus 9.0 months.

Verastem, the manufacturer of duvelisib, plans to present the complete findings from DUO at a future medical meeting and submit the data for publication in a peer-reviewed journal.

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The FDA has extended its decision deadline by 3 months on a biologics license application for the trastuzumab biosimilar MYL-1401O. Under the new timeframe, a final decision is expected on or before December 3, 2017.

The companies submitted the BLA to the FDA in November 2016, with an original action deadline of September 3, 2017. In July 2017, the FDA’s Oncologic Drugs Advisory Committee voted 16-0 to recommend approval of MYL-1401O.

The FDA notified Mylan and Biocon, the developers of the biosimilar, that the extension was made to review clarificatory information submitted to them as a part of the application review process.

If approved, MYL-1401O would be licensed in the United States as a treatment for adjuvant breast cancer, metastatic breast cancer, and metastatic gastric cancer, the same indications as trastuzumab. Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication. The companies cannot market the drug for that purpose until the exclusive license expires.

The BLA includes phase III results from the 2-part, multicenter randomized HERiTage study, in which patients were randomized to MYL-1401O plus a taxane or trastuzumab with a taxane. Results showed that in part 2 of the study, the difference in overall response rate was 6% and progression-free survival was nearly identical between the 2 arms. Median overall survival had not been met in either group.

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

A clinical hold has been placed by the FDA on 2 phase I trials exploring the gene-edited allogeneic CAR T-cell therapy UCART123.

The decision follows the death of a 78-year-old man being treated for blastic plasmacytoid dendritic cell neoplasm who experienced cytokine release syndrome CRS. A 58-year-old woman with AML who was also being treated with the therapy developed CRS; however, her condition resolved. Both patients were the first to be treated in their respective trials.

UCART123 is being developed by the Paris-based biopharmaceutical company Cellectis as a treatment for BPDCN and AML. Unlike Novartis’s autologous CAR-T therapy tisagenlecleucel UCART’s process is allogeneic and theoretically could treat any patient using T cells harvested from any donor.

The off-the-shelf allogenic process may be faster, easier to develop, and likely significantly less expensive than autologous CAR T-cell therapy—Novartis has set the price for a one-time treatment with tisagenlecleucel at $475,000.

In a press release, Cellectis reported that it is working with the FDA in order to resume the trials with an amended protocol, including a reduced dose of UCART123 cells.

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

In urothelial carcinoma, the European Commission has approved pembrolizumab for the treatment of patients with locally advanced or metastatic disease who have received prior platinum-containing chemotherapy, or who are not eligible for cisplatin-containing chemotherapy.

The frontline approval for cisplatin-ineligible patients was based on the results of the phase II KEYNOTE-052 trial, in which the overall response rate was 29% with a clinical benefit rate of 47%.

The second-line approval was based on the phase III KEYNOTE-045 study, in which pembrolizumab reduced the risk of death by 27% versus chemotherapy in patients with advanced urothelial carcinoma whose disease progressed after prior treatment.

The European Commission’s decision follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The PD-1 inhibitor can now be marketed for these 2 new indications in all 28 EU member states plus Iceland, Lichtenstein, and Norway.

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

This week, we sat down with Dr Mark Soberman, president of the Association of Community Cancer Centers to discuss his presidential theme of next-generation multidisciplinary care for patients with cancer.

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 acute myeloid leukemia, a new drug application submitted in multiple myeloma, encouraging results in a chronic lymphocytic leukemia trial, a delayed decision on a biosimilar, a clinical hold on CAR T-cell therapy trials, and a European approval in bladder cancer.

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

The FDA has approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia.

The antibody-drug conjugate was also approved for the treatment of patients aged 2 years and older with CD33-positive relapsed/refractory AML. The decision follows the recommendation of the FDA’s Oncologic Drugs Advisory Committee, which voted 6 to 1 recommending approval during a meeting this past July.  

The decision was based on data from a number of trials, including the ALFA-0701, AML-19, and MyloFrance-1.1 trials. In ALFA-0701, gemtuzumab ozogamicin was associated with a statistically significant improvement in event-free survival of 7.8 months. However, the drug was not associated with a significant improvement in overall survival.

In Study AML-19, the agent was associated with a reduction in the risk of death by 31%, as well as a median OS of 4.9 months versus 3.6 months in the control arm.

The label for gemtuzumab ozogamicin includes a boxed warning for hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome.

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

In multiple myeloma, the FDA has accepted a supplemental new drug application seeking to add overall survival data from the phase III ENDEAVOR trial to the label for carfilzomib for use in patients with relapsed or refractory disease.

The primary OS analysis from ENDEAVOR showed that carfilzomib reduced the risk of death by 21% versus bortezomib. Moreover, carfilzomib plus dexamethasone was found to extend overall survival by 7.6 months versus bortezomib combined with dexamethasone.

Currently, carfilzomib is approved in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy. The treatment is also approved as a monotherapy for relapsed/refractory patients who have received 1 or more lines of therapy.

The Prescription Drug User Fee Act action date for the FDA’s decision on the label update is April 30, 2018.

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

The PI3K-delta and –gamma inhibitor duvelisib was found to reduce the risk of disease progression or death by 48% versus ofatumumab in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who were enrolled in the phase III DUO trial.

Findings showed that, in the overall population, the median progression-free survival with duvelisib was 3.4 months longer compared with ofatumumab. In patients with a 17p deletion, the median PFS benefit was 3.7 months.

The median PFS was 13.3 months in the duvelisib arm compared with 9.9 months in the ofatumumab arm. In patients with a 17p deletion, the median PFS was 12.7 versus 9.0 months.

Verastem, the manufacturer of duvelisib, plans to present the complete findings from DUO at a future medical meeting and submit the data for publication in a peer-reviewed journal.

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

The FDA has extended its decision deadline by 3 months on a biologics license application for the trastuzumab biosimilar MYL-1401O. Under the new timeframe, a final decision is expected on or before December 3, 2017.

The companies submitted the BLA to the FDA in November 2016, with an original action deadline of September 3, 2017. In July 2017, the FDA’s Oncologic Drugs Advisory Committee voted 16-0 to recommend approval of MYL-1401O.

The FDA notified Mylan and Biocon, the developers of the biosimilar, that the extension was made to review clarificatory information submitted to them as a part of the application review process.

If approved, MYL-1401O would be licensed in the United States as a treatment for adjuvant breast cancer, metastatic breast cancer, and metastatic gastric cancer, the same indications as trastuzumab. Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication. The companies cannot market the drug for that purpose until the exclusive license expires.

The BLA includes phase III results from the 2-part, multicenter randomized HERiTage study, in which patients were randomized to MYL-1401O plus a taxane or trastuzumab with a taxane. Results showed that in part 2 of the study, the difference in overall response rate was 6% and progression-free survival was nearly identical between the 2 arms. Median overall survival had not been met in either group.

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

A clinical hold has been placed by the FDA on 2 phase I trials exploring the gene-edited allogeneic CAR T-cell therapy UCART123.

The decision follows the death of a 78-year-old man being treated for blastic plasmacytoid dendritic cell neoplasm who experienced cytokine release syndrome CRS. A 58-year-old woman with AML who was also being treated with the therapy developed CRS; however, her condition resolved. Both patients were the first to be treated in their respective trials.

UCART123 is being developed by the Paris-based biopharmaceutical company Cellectis as a treatment for BPDCN and AML. Unlike Novartis’s autologous CAR-T therapy tisagenlecleucel UCART’s process is allogeneic and theoretically could treat any patient using T cells harvested from any donor.

The off-the-shelf allogenic process may be faster, easier to develop, and likely significantly less expensive than autologous CAR T-cell therapy—Novartis has set the price for a one-time treatment with tisagenlecleucel at $475,000.

In a press release, Cellectis reported that it is working with the FDA in order to resume the trials with an amended protocol, including a reduced dose of UCART123 cells.

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

In urothelial carcinoma, the European Commission has approved pembrolizumab for the treatment of patients with locally advanced or metastatic disease who have received prior platinum-containing chemotherapy, or who are not eligible for cisplatin-containing chemotherapy.

The frontline approval for cisplatin-ineligible patients was based on the results of the phase II KEYNOTE-052 trial, in which the overall response rate was 29% with a clinical benefit rate of 47%.

The second-line approval was based on the phase III KEYNOTE-045 study, in which pembrolizumab reduced the risk of death by 27% versus chemotherapy in patients with advanced urothelial carcinoma whose disease progressed after prior treatment.

The European Commission’s decision follows a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use.

The PD-1 inhibitor can now be marketed for these 2 new indications in all 28 EU member states plus Iceland, Lichtenstein, and Norway.

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

This week, we sat down with Dr Mark Soberman, president of the Association of Community Cancer Centers to discuss his presidential theme of next-generation multidisciplinary care for patients with cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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Medical Crossfire®: Redefining Treatment Paradigms in the Management of Chronic Lymphocytic LeukemiaOct 05, 20172.0
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