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FDA Approvals in MCL and Beta Thalessemia-Associated Anemia, Priority Review in HCC, and More

Gina Columbus
Published: Monday, Nov 18, 2019



Today-

FDA approvals in mantle cell lymphoma and beta thalassemia–associated anemia, a priority review designation in hepatocellular carcinoma, encouraging findings in graft-versus-host disease, and disappointing findings in a biliary tract cancer trial.

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

The FDA has granted an accelerated approval to zanubrutinib, known by the trade name Brukinsa, for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy.

The approval occurred more than 3 months ahead of the FDA's action date. It is based on data from two single-arm studies, in which zanubrutinib elicited an overall response rate of 84% in patients with MCL who received ≥1 prior treatment.

In a single-arm, phase II Chinese trial, the ORR comprised a 59% complete response rate and a 24% partial response rate at a median follow-up of 18.4 months. Additionally, the median duration of response was 19.5 months.

In the second study, a phase I/II trial, the 84% ORR included a 22% CR rate and a 62% PR rate. At a median follow-up of 18.8 months, the median DOR was 18.5 months.

Zanubrutinib is a small molecule BTK inhibitor that has been investigated alone and in combination to treat patients with a wide range of B-cell malignancies. Its accelerated approval is contingent on the results of a confirmatory trial.

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The FDA has approved luspatercept-aamt, known by the trade name Reblozyl, for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.

The approval is based on findings from the phase III BELIEVE study, which showed that treatment with luspatercept-aamt led to significant reductions in RBC transfusion burden in this patient population.

Results specifically showed that 21.4% of patients who received luspatercept-aamt achieved at least a 33% reduction from baseline in RBC transfusion burden, with a reduction of 2 or more units, during weeks 13 to 24 after randomization compared with 4.5% of patients who received placebo.

The FDA is also evaluating luspatercept-aamt for the treatment of anemia in adult patients with very low- to intermediate-risk myelodysplastic syndromes who have ring sideroblasts and require RBC transfusions. The agency must decide on the approval of the erythroid maturation agent for this indication by April 4, 2020.

In Europe, the Marketing Authorization Application for luspatercept-aamt for the treatment of anemia in adults with beta thalassemia or MDS is currently being reviewed.

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

In hepatocellular carcinoma, the FDA has granted a priority review designation to a supplemental biologics license application for the combination of nivolumab and ipilimumab for the treatment of patients with advanced disease who received prior sorafenib. The FDA also granted a breakthrough therapy designation to the combination for use in this setting.

The designation is based on results of a cohort from the phase I/II CheckMate-040 study, in which nivolumab and ipilimumab were evaluated in this patient population at varying doses. Results recently showed that across 3 dosing schedules, the objective response rate with the combination was 31%.

Additionally, the median duration of response was 17 months, the disease control rate was 49%, and the 2-year overall survival rate was 40%. Regarding safety, the combination was found to be well tolerated.

The FDA must make a decision on the application by March 10, 2020. Nivolumab is currently indicated for the treatment of patients with HCC who have been previously treated with sorafenib.

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

Treatment with the selective ROCK2 inhibitor KD025 elicited statistically significant overall response rates in patients with chronic graft-versus-host disease who have received 2 or more prior lines of systemic therapy, meeting the primary endpoint at an interim analysis of the phase II ROCKstar trial.

At the 200-mg once-daily dose, KD025 elicited an ORR of 64%, and the 200-mg twice-daily schedule led to a 67% ORR in this patient population. Statistical significance was achieved if the lower bound of the 95% confidence interval of ORR was greater than 30%. Additionally, the therapy has been well tolerated.

Kadmon Holdings, the manufacturer of KD025, stated in a press release that it will be sharing the ORR findings at a pre–new drug application meeting with the FDA.

The company also noted that while the ORR endpoint was met at the interim analysis, the primary analysis of the trial will occur in the first quarter of 2020, which will be 6 months after completion of enrollment. The primary analysis will include updated safety and efficacy findings, including ORRs, duration of response, changes in corticosteroid dose, and changes in quality of life. These data will be presented at an upcoming scientific meeting.

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

In biliary tract cancer, results of the TreeTopp trial showed that varlitinib combined with capecitabine did not improve progression-free survival or overall response rate versus capecitabine plus placebo as a second-line treatment, missing both primary endpoints of the study.

Varlitinib is a highly potent, oral, reversible, small molecule pan-HER inhibitor that targets HER1, HER2, and HER4, which can be mutated or overexpressed in many cancers.

Results specifically showed that the median PFS was 2.83 months in the varlitinib arm versus 2.79 months in the control arm, and the ORRs was 9.4% and 4.8%, respectively; neither endpoint of which reached statistical significance. The safety data were consistent with the known tolerability of varlitinib.

However, pre-planned exploratory analyses did identify a subgroup of patients in which varlitinib demonstrated improved efficacy. Further analyses of those findings are ongoing.

ASLAN Pharmaceuticals, the manufacturer of varlitinib, stated that it will now instead focus on development of ASLAN004, an IL-4/IL-13 blocker monoclonal antibody.

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

This week, we sat down with Dr Alicia Morgans, of Northwestern University Feinberg School of Medicine, to discuss new overall survival data in treatment for nonmetastatic castration-resistant prostate 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 mantle cell lymphoma and beta thalassemia–associated anemia, a priority review designation in hepatocellular carcinoma, encouraging findings in graft-versus-host disease, and disappointing findings in a biliary tract cancer trial.

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

The FDA has granted an accelerated approval to zanubrutinib, known by the trade name Brukinsa, for the treatment of adult patients with mantle cell lymphoma who have received at least 1 prior therapy.

The approval occurred more than 3 months ahead of the FDA's action date. It is based on data from two single-arm studies, in which zanubrutinib elicited an overall response rate of 84% in patients with MCL who received ≥1 prior treatment.

In a single-arm, phase II Chinese trial, the ORR comprised a 59% complete response rate and a 24% partial response rate at a median follow-up of 18.4 months. Additionally, the median duration of response was 19.5 months.

In the second study, a phase I/II trial, the 84% ORR included a 22% CR rate and a 62% PR rate. At a median follow-up of 18.8 months, the median DOR was 18.5 months.

Zanubrutinib is a small molecule BTK inhibitor that has been investigated alone and in combination to treat patients with a wide range of B-cell malignancies. Its accelerated approval is contingent on the results of a confirmatory trial.

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

The FDA has approved luspatercept-aamt, known by the trade name Reblozyl, for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell transfusions.

The approval is based on findings from the phase III BELIEVE study, which showed that treatment with luspatercept-aamt led to significant reductions in RBC transfusion burden in this patient population.

Results specifically showed that 21.4% of patients who received luspatercept-aamt achieved at least a 33% reduction from baseline in RBC transfusion burden, with a reduction of 2 or more units, during weeks 13 to 24 after randomization compared with 4.5% of patients who received placebo.

The FDA is also evaluating luspatercept-aamt for the treatment of anemia in adult patients with very low- to intermediate-risk myelodysplastic syndromes who have ring sideroblasts and require RBC transfusions. The agency must decide on the approval of the erythroid maturation agent for this indication by April 4, 2020.

In Europe, the Marketing Authorization Application for luspatercept-aamt for the treatment of anemia in adults with beta thalassemia or MDS is currently being reviewed.

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

In hepatocellular carcinoma, the FDA has granted a priority review designation to a supplemental biologics license application for the combination of nivolumab and ipilimumab for the treatment of patients with advanced disease who received prior sorafenib. The FDA also granted a breakthrough therapy designation to the combination for use in this setting.

The designation is based on results of a cohort from the phase I/II CheckMate-040 study, in which nivolumab and ipilimumab were evaluated in this patient population at varying doses. Results recently showed that across 3 dosing schedules, the objective response rate with the combination was 31%.

Additionally, the median duration of response was 17 months, the disease control rate was 49%, and the 2-year overall survival rate was 40%. Regarding safety, the combination was found to be well tolerated.

The FDA must make a decision on the application by March 10, 2020. Nivolumab is currently indicated for the treatment of patients with HCC who have been previously treated with sorafenib.

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

Treatment with the selective ROCK2 inhibitor KD025 elicited statistically significant overall response rates in patients with chronic graft-versus-host disease who have received 2 or more prior lines of systemic therapy, meeting the primary endpoint at an interim analysis of the phase II ROCKstar trial.

At the 200-mg once-daily dose, KD025 elicited an ORR of 64%, and the 200-mg twice-daily schedule led to a 67% ORR in this patient population. Statistical significance was achieved if the lower bound of the 95% confidence interval of ORR was greater than 30%. Additionally, the therapy has been well tolerated.

Kadmon Holdings, the manufacturer of KD025, stated in a press release that it will be sharing the ORR findings at a pre–new drug application meeting with the FDA.

The company also noted that while the ORR endpoint was met at the interim analysis, the primary analysis of the trial will occur in the first quarter of 2020, which will be 6 months after completion of enrollment. The primary analysis will include updated safety and efficacy findings, including ORRs, duration of response, changes in corticosteroid dose, and changes in quality of life. These data will be presented at an upcoming scientific meeting.

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

In biliary tract cancer, results of the TreeTopp trial showed that varlitinib combined with capecitabine did not improve progression-free survival or overall response rate versus capecitabine plus placebo as a second-line treatment, missing both primary endpoints of the study.

Varlitinib is a highly potent, oral, reversible, small molecule pan-HER inhibitor that targets HER1, HER2, and HER4, which can be mutated or overexpressed in many cancers.

Results specifically showed that the median PFS was 2.83 months in the varlitinib arm versus 2.79 months in the control arm, and the ORRs was 9.4% and 4.8%, respectively; neither endpoint of which reached statistical significance. The safety data were consistent with the known tolerability of varlitinib.

However, pre-planned exploratory analyses did identify a subgroup of patients in which varlitinib demonstrated improved efficacy. Further analyses of those findings are ongoing.

ASLAN Pharmaceuticals, the manufacturer of varlitinib, stated that it will now instead focus on development of ASLAN004, an IL-4/IL-13 blocker monoclonal antibody.

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

This week, we sat down with Dr Alicia Morgans, of Northwestern University Feinberg School of Medicine, to discuss new overall survival data in treatment for nonmetastatic castration-resistant prostate cancer.

That’s all for today.

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