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FDA Approvals in Myeloma, NSCLC, and of a Biosimilar, Priority Review in Gastric Cancer, and More

Gina Columbus
Published: Monday, Nov 12, 2018



Today-

FDA approvals in multiple myeloma, non–small cell lung cancer, and of a biosimilar, priority reviews in graft-versus-host disease and gastric cancer, and a supplemental biologics application submitted in peripheral T-cell lymphoma.

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

The FDA has approved elotuzumab for use in combination with pomalidomide and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma following 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

The decision was based on data from the phase II ELOQUENT-3 trial, in which the addition of elotuzumab to pomalidomide and dexamethasone reduced the risk of disease progression or death by 46% versus pomalidomide and dexamethasone alone for patients with relapsed/refractory disease.

In the ELOQUENT-3 study, the median progression-free survival was 10.3 months with the elotuzumab triplet compared with 4.7 months with pomalidomide plus dexamethasone. The PFS benefit associated with the elotuzumab regimen was similar, regardless of whether patients received 2 to 3 prior lines of treatment or more than 4 lines of treatment.

The objective response rate was 53% with elotuzumab compared with 26% in the control arm. The rate of very good partial response or better was 20% versus 9%, with and without elotuzumab, respectively.

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

The FDA has granted lorlatinib, known by the trade name Lorbrena, an accelerated approval for the treatment of patients with ALK-positive metastatic non–small cell lung cancer who have progressed on 1 or more ALK tyrosine kinase inhibitors.

Lorlatinib is specifically approved for patients who have progressed on crizotinib and at least 1 other ALK inhibitor for metastatic disease.

The approval is based on a nonrandomized, dose-ranging, multicohort, multicenter phase II study that included a subgroup of 215 patients with ALK-positive metastatic NSCLC previously treated with more than 1 ALK kinase inhibitor. Results showed that the overall response rate with lorlatinib in these patients was 48%, including a complete response rate of 4% and a partial response rate of 44%. The median duration of response was 12.5 months.

The FDA-recommended dose of lorlatinib is 100 mg orally once daily. Moreover, the accelerated approval of lorlatinib in this setting is contingent on the results of a confirmatory trial.

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Also in non–small cell lung cancer, the FDA has approved pembrolizumab for use in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous non–small cell lung cancer.

The approval is based on data from the phase III KEYNOTE-407 trial, in which the immunotherapy combination reduced the risk of death by 36% versus chemotherapy alone in patients with metastatic squamous NSCLC. The median overall survival was 15.9 months with pembrolizumab versus 11.3 months with chemotherapy alone. The OS benefit was observed across patient subgroups.

Moreover, the median PFS was 6.4 months with the PD-1 inhibitor versus 4.8 months with chemotherapy alone. While the PFS benefit was also observed across all PD-L1 expression levels, there was a correlation between an increase in PD-L1 level and a greater magnitude of benefit.

The objective response rate in the pembrolizumab arm was 58% compared with 35% in the control arm. The median duration of response was 7.2 months versus 4.9 months in the pembrolizumab versus placebo arms, respectively.

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

In graft-versus-host disease, the FDA granted a priority review designation to a supplemental new drug application for ruxolitinib for the treatment of patients with acute disease who have had an inadequate response to corticosteroids.

The application is based on findings from the pivotal phase II REACH1 trial, in which ruxolitinib combined with corticosteroids induced an overall response rate of 55% at day 28 in patients with steroid-refractory acute GVHD, which met the primary endpoint of the study. Results also showed that 39 of 71 patients achieved an objective response at day 28.

Additionally, 52 patients had a response at any time point in the study, translating to a best overall response rate of 73%. The most frequently reported treatment-related adverse events across all grades included anemia, thrombocytopenia, and neutropenia.

Incyte, the manufacturer of ruxolitinib, reported in a news release that the full data from REACH1 will be presented at an upcoming medical conference. In the single-arm phase II REACH1 study, patients with steroid-refractory acute GVHD received ruxolitinib in combination with investigator’s choice of oral prednisone or intravenous methylprednisolone.

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

The FDA has granted a priority review to a supplemental new drug application for TAS-102 for use in previously treated patients with advanced or metastatic gastric adenocarcinoma, including cancer of the gastroesophageal junction.

The sNDA is based on findings from the phase III TAGS trial, in which TAS-102 reduced the risk of death by approximately one-third versus placebo in patients with heavily pretreated gastric or GEJ cancer. The TAGS study also showed improvements in progression-free survival and disease control, and demonstrated a predictable and manageable safety profile.

Results showed that overall survival was 5.7 months for patients assigned to TAS-102 compared with 3.6 months for patients randomized to placebo. The 2.1-month improvement in median OS with TAS-102 over placebo translated into a hazard ratio for death of 0.69.

Additionally, the median progression-free survival was also significantly improved with TAS-102 compared with placebo at 2.0 versus 1.8 months, respectively. Also, the objective response rate with TAS-102 was 4% compared with 2% for placebo.

Under the Prescription Drug User Fee Act, the agency is scheduled to make a decision on the application by February 24, 2019.

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

In peripheral T-cell lymphoma, a supplemental biologics license application was submitted to the FDA for the use of brentuximab vedotin plus chemotherapy for the frontline treatment of patients with CD30-expressing disease.

The application is based on the phase III ECHELON-2 trial, which showed that the combination of frontline brentuximab vedotin with the CHP regimen of cyclophosphamide, doxorubicin, and prednisone reduced the risk of death by 34% and the risk of disease progression or death by 29% compared with the standard CHOP regimen.

Seattle Genetics and Takeda Pharmaceutical, the co-developers of brentuximab vedotin, will be presenting additional ECHELON-2 findings at the 2018 ASH Annual Meeting.

In ECHELON-2, progression-free survival per independent review was the primary endpoint, with secondary endpoints including overall survival, PFS in patients with systemic anaplastic large cell lymphoma; objective response rate, complete remission rate, and safety.

Seattle Genetics and Takeda stated that all secondary endpoints were also met, and the safety profile was similar between the 2 study arms with no new safety signals emerging with brentuximab vedotin.

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

This week, we sat down with Dr Sai-Hong Ignatius Ou, of the University of California, Irvine, to discuss osimertinib against uncommon EGFR mutations in non–small cell lung cancer.

That’s all for today.

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

FDA approvals in multiple myeloma, non–small cell lung cancer, and of a biosimilar, priority reviews in graft-versus-host disease and gastric cancer, and a supplemental biologics application submitted in peripheral T-cell lymphoma.

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

The FDA has approved elotuzumab for use in combination with pomalidomide and low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma following 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

The decision was based on data from the phase II ELOQUENT-3 trial, in which the addition of elotuzumab to pomalidomide and dexamethasone reduced the risk of disease progression or death by 46% versus pomalidomide and dexamethasone alone for patients with relapsed/refractory disease.

In the ELOQUENT-3 study, the median progression-free survival was 10.3 months with the elotuzumab triplet compared with 4.7 months with pomalidomide plus dexamethasone. The PFS benefit associated with the elotuzumab regimen was similar, regardless of whether patients received 2 to 3 prior lines of treatment or more than 4 lines of treatment.

The objective response rate was 53% with elotuzumab compared with 26% in the control arm. The rate of very good partial response or better was 20% versus 9%, with and without elotuzumab, respectively.

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

The FDA has granted lorlatinib, known by the trade name Lorbrena, an accelerated approval for the treatment of patients with ALK-positive metastatic non–small cell lung cancer who have progressed on 1 or more ALK tyrosine kinase inhibitors.

Lorlatinib is specifically approved for patients who have progressed on crizotinib and at least 1 other ALK inhibitor for metastatic disease.

The approval is based on a nonrandomized, dose-ranging, multicohort, multicenter phase II study that included a subgroup of 215 patients with ALK-positive metastatic NSCLC previously treated with more than 1 ALK kinase inhibitor. Results showed that the overall response rate with lorlatinib in these patients was 48%, including a complete response rate of 4% and a partial response rate of 44%. The median duration of response was 12.5 months.

The FDA-recommended dose of lorlatinib is 100 mg orally once daily. Moreover, the accelerated approval of lorlatinib in this setting is contingent on the results of a confirmatory trial.

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

Also in non–small cell lung cancer, the FDA has approved pembrolizumab for use in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of patients with metastatic squamous non–small cell lung cancer.

The approval is based on data from the phase III KEYNOTE-407 trial, in which the immunotherapy combination reduced the risk of death by 36% versus chemotherapy alone in patients with metastatic squamous NSCLC. The median overall survival was 15.9 months with pembrolizumab versus 11.3 months with chemotherapy alone. The OS benefit was observed across patient subgroups.

Moreover, the median PFS was 6.4 months with the PD-1 inhibitor versus 4.8 months with chemotherapy alone. While the PFS benefit was also observed across all PD-L1 expression levels, there was a correlation between an increase in PD-L1 level and a greater magnitude of benefit.

The objective response rate in the pembrolizumab arm was 58% compared with 35% in the control arm. The median duration of response was 7.2 months versus 4.9 months in the pembrolizumab versus placebo arms, respectively.

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

In graft-versus-host disease, the FDA granted a priority review designation to a supplemental new drug application for ruxolitinib for the treatment of patients with acute disease who have had an inadequate response to corticosteroids.

The application is based on findings from the pivotal phase II REACH1 trial, in which ruxolitinib combined with corticosteroids induced an overall response rate of 55% at day 28 in patients with steroid-refractory acute GVHD, which met the primary endpoint of the study. Results also showed that 39 of 71 patients achieved an objective response at day 28.

Additionally, 52 patients had a response at any time point in the study, translating to a best overall response rate of 73%. The most frequently reported treatment-related adverse events across all grades included anemia, thrombocytopenia, and neutropenia.

Incyte, the manufacturer of ruxolitinib, reported in a news release that the full data from REACH1 will be presented at an upcoming medical conference. In the single-arm phase II REACH1 study, patients with steroid-refractory acute GVHD received ruxolitinib in combination with investigator’s choice of oral prednisone or intravenous methylprednisolone.

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

The FDA has granted a priority review to a supplemental new drug application for TAS-102 for use in previously treated patients with advanced or metastatic gastric adenocarcinoma, including cancer of the gastroesophageal junction.

The sNDA is based on findings from the phase III TAGS trial, in which TAS-102 reduced the risk of death by approximately one-third versus placebo in patients with heavily pretreated gastric or GEJ cancer. The TAGS study also showed improvements in progression-free survival and disease control, and demonstrated a predictable and manageable safety profile.

Results showed that overall survival was 5.7 months for patients assigned to TAS-102 compared with 3.6 months for patients randomized to placebo. The 2.1-month improvement in median OS with TAS-102 over placebo translated into a hazard ratio for death of 0.69.

Additionally, the median progression-free survival was also significantly improved with TAS-102 compared with placebo at 2.0 versus 1.8 months, respectively. Also, the objective response rate with TAS-102 was 4% compared with 2% for placebo.

Under the Prescription Drug User Fee Act, the agency is scheduled to make a decision on the application by February 24, 2019.

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

In peripheral T-cell lymphoma, a supplemental biologics license application was submitted to the FDA for the use of brentuximab vedotin plus chemotherapy for the frontline treatment of patients with CD30-expressing disease.

The application is based on the phase III ECHELON-2 trial, which showed that the combination of frontline brentuximab vedotin with the CHP regimen of cyclophosphamide, doxorubicin, and prednisone reduced the risk of death by 34% and the risk of disease progression or death by 29% compared with the standard CHOP regimen.

Seattle Genetics and Takeda Pharmaceutical, the co-developers of brentuximab vedotin, will be presenting additional ECHELON-2 findings at the 2018 ASH Annual Meeting.

In ECHELON-2, progression-free survival per independent review was the primary endpoint, with secondary endpoints including overall survival, PFS in patients with systemic anaplastic large cell lymphoma; objective response rate, complete remission rate, and safety.

Seattle Genetics and Takeda stated that all secondary endpoints were also met, and the safety profile was similar between the 2 study arms with no new safety signals emerging with brentuximab vedotin.

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

This week, we sat down with Dr Sai-Hong Ignatius Ou, of the University of California, Irvine, to discuss osimertinib against uncommon EGFR mutations in non–small cell lung cancer.

That’s all for today.

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