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Priority Review Designation in GIST, Promising Findings in Bladder Cancer and NSCLC, and More

Gina Columbus
Published: Tuesday, Aug 20, 2019



Today-

A priority review designation and encouraging findings in gastrointestinal stromal tumors, promising data in bladder cancer and lung cancer, and European indications expanded in chronic lymphocytic leukemia and Waldenström macroglobulinemia.

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

The FDA has granted a priority review designation to a new drug application for avapritinib for the treatment of adult patients with PDGFRA exon 18–mutant gastrointestinal stromal tumors, regardless of prior therapy, as well as for patients with GIST in the fourth-line setting.

Avapritinib has been evaluated in the open-label, dose-escalation/dose-expansion phase I NAVIGATOR trial, which explored the activity of the agent at the recommended phase II dose of 300 mg once daily and the maximum-tolerated dose of 400 mg daily in patients with GIST who had PDGFRA exon 18 mutations or in the fourth-line setting.

In the PDGFRA exon 18–mutant cohort, the ORR was 86.0%. The clinical benefit rate was 95.3%, while the median duration of response and median progression-free survival was not estimated.

In the fourth-line cohort, data showed that the ORR was 22%, the CBR was 41%, the median DOR was 10.2 months, and the median PFS was 3.7 months at a median follow-up of 10.8 months.

The FDA must make a decision on the NDA by February 14, 2020.

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Also in gastrointestinal stromal tumors, ripretinib improved progression-free survival compared with placebo in patients with fourth-line and fourth-line plus advanced disease, according to topline findings of the phase III INVICTUS study.

In the trial, the broad-spectrum KIT and PDGFRα inhibitor led to a median PFS of 6.3 months compared with 1.0 months with placebo in this patient population, translating to an 85% reduction in the risk of disease progression or death.

Additional data showed that the ORR was 9.4% with ripretinib compared with 0% for placebo, which was not found to be statistically significant. Moreover, ripretinib did show a clinically meaningful improvement in OS versus placebo at 15.1 months compared with 6.6 months, respectively.

However, since the statistical significance for ORR was not achieved, the hypothesis testing of OS was not formally performed due to a prespecified hierarchical testing procedure of the endpoints. In the placebo arm, the OS data included patients who crossed over to receive ripretinib following disease progression.

Deciphera, the manufacturer of ripretinib, plans to submit a new drug application to the FDA in the first quarter of 2020 based on these data. The NDA would allow ripretinib to be used as a treatment for patients with advanced GIST who previously received imatinib, sunitinib, and regorafenib.

Full findings from the INVICTUS study are expected to be presented at an upcoming medical meeting.

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

In the phase III VISTA trial, vicinium led to encouraging 6- and 12-month complete response rates in patients with high-risk non-muscle invasive bladder cancer who did not respond to Bacillus Calmette-Guérin therapy.

Across 2 of the 3 patient cohorts, the 6-month CR rate was 28% and the 12-month CR rate was 17% in patients with carcinoma in situ who had received prior BCG therapy.

Updated safety findings also showed that 95% of all adverse events were of grade 1 or 2, and serious AEs were observed in 14% of patients. Four patients discontinued treatment due to an AE.

These data will serve as the basis for a biologics license application that will likely be submitted to the FDA in the fourth quarter of 2019. Following the submission, the company stated that an Oncologic Drugs Advisory Committee meeting is expected to take place to review the risk-benefit profile of Vicinium.

The FDA granted a fast track designation to Vicinium in August 2019 for the treatment of patients with BCG-unresponsive, high-grade NMIBC.

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

In non–small cell lung cancer, frontline osimertinib significantly improved overall survival compared with erlotinib or gefitinib in patients with EGFR-positive local advanced or metastatic non–small cell lung cancer, according to results from the phase III FLAURA trial.

AstraZeneca, the manufacturer of the third-generation EGFR inhibitor, reported in a press release that the OS data will be presented at an upcoming medical conference.

Prior data from FLAURA showed that frontline osimertinib reduced the risk of progression or death by 54% versus erlotinib or gefitinib. In the double-blind study, the median PFS was 10.2 months for standard therapy and 18.9 months with osimertinib. The PFS benefit with osimertinib extended across all prespecified subgroups.

Additionally, the objective response rate with osimertinib was 77% compared with 69% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.6 months versus 9.6 months in the comparator arm.

Based on these PFS data from FLAURA, the FDA approved osimertinib in April 2018 for use in this setting.

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

The European Commission has expanded the approval of ibrutinib to include use in combination with obinutuzumab for adult patients with previously untreated chronic lymphocytic leukemia, and also in combination with rituximab for the treatment of adult patients with Waldenström macroglobulinemia.

The expanded indications stem from a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use in June 2018.

The approval for the expanded indication in CLL is based on results of the phase III iLLUMINATE study, which showed that the combination led to a 77% reduction in the risk of progression or death versus chlorambucil plus obinutuzumab in patients with CLL or small lymphocytic lymphoma.

For the recommendation in the WM indication, the approval was based on data from the phase III iNNOVATE trial, which showed that the combination had an estimated 30-month PFS rate, which was assessed by an independent review committee, of 79% compared with 41% for those who received rituximab/placebo in patients with previously untreated and relapsed/refractory WM, at a median follow-up of 30.4 months.

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

This week, we sat down with Rafat Abonour, MD, Indiana University Health, to discuss optimizing therapy for patients with multiple myeloma.

That’s all for today.

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

A priority review designation and encouraging findings in gastrointestinal stromal tumors, promising data in bladder cancer and lung cancer, and European indications expanded in chronic lymphocytic leukemia and Waldenström macroglobulinemia.

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

The FDA has granted a priority review designation to a new drug application for avapritinib for the treatment of adult patients with PDGFRA exon 18–mutant gastrointestinal stromal tumors, regardless of prior therapy, as well as for patients with GIST in the fourth-line setting.

Avapritinib has been evaluated in the open-label, dose-escalation/dose-expansion phase I NAVIGATOR trial, which explored the activity of the agent at the recommended phase II dose of 300 mg once daily and the maximum-tolerated dose of 400 mg daily in patients with GIST who had PDGFRA exon 18 mutations or in the fourth-line setting.

In the PDGFRA exon 18–mutant cohort, the ORR was 86.0%. The clinical benefit rate was 95.3%, while the median duration of response and median progression-free survival was not estimated.

In the fourth-line cohort, data showed that the ORR was 22%, the CBR was 41%, the median DOR was 10.2 months, and the median PFS was 3.7 months at a median follow-up of 10.8 months.

The FDA must make a decision on the NDA by February 14, 2020.

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

Also in gastrointestinal stromal tumors, ripretinib improved progression-free survival compared with placebo in patients with fourth-line and fourth-line plus advanced disease, according to topline findings of the phase III INVICTUS study.

In the trial, the broad-spectrum KIT and PDGFRα inhibitor led to a median PFS of 6.3 months compared with 1.0 months with placebo in this patient population, translating to an 85% reduction in the risk of disease progression or death.

Additional data showed that the ORR was 9.4% with ripretinib compared with 0% for placebo, which was not found to be statistically significant. Moreover, ripretinib did show a clinically meaningful improvement in OS versus placebo at 15.1 months compared with 6.6 months, respectively.

However, since the statistical significance for ORR was not achieved, the hypothesis testing of OS was not formally performed due to a prespecified hierarchical testing procedure of the endpoints. In the placebo arm, the OS data included patients who crossed over to receive ripretinib following disease progression.

Deciphera, the manufacturer of ripretinib, plans to submit a new drug application to the FDA in the first quarter of 2020 based on these data. The NDA would allow ripretinib to be used as a treatment for patients with advanced GIST who previously received imatinib, sunitinib, and regorafenib.

Full findings from the INVICTUS study are expected to be presented at an upcoming medical meeting.

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

In the phase III VISTA trial, vicinium led to encouraging 6- and 12-month complete response rates in patients with high-risk non-muscle invasive bladder cancer who did not respond to Bacillus Calmette-Guérin therapy.

Across 2 of the 3 patient cohorts, the 6-month CR rate was 28% and the 12-month CR rate was 17% in patients with carcinoma in situ who had received prior BCG therapy.

Updated safety findings also showed that 95% of all adverse events were of grade 1 or 2, and serious AEs were observed in 14% of patients. Four patients discontinued treatment due to an AE.

These data will serve as the basis for a biologics license application that will likely be submitted to the FDA in the fourth quarter of 2019. Following the submission, the company stated that an Oncologic Drugs Advisory Committee meeting is expected to take place to review the risk-benefit profile of Vicinium.

The FDA granted a fast track designation to Vicinium in August 2019 for the treatment of patients with BCG-unresponsive, high-grade NMIBC.

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

In non–small cell lung cancer, frontline osimertinib significantly improved overall survival compared with erlotinib or gefitinib in patients with EGFR-positive local advanced or metastatic non–small cell lung cancer, according to results from the phase III FLAURA trial.

AstraZeneca, the manufacturer of the third-generation EGFR inhibitor, reported in a press release that the OS data will be presented at an upcoming medical conference.

Prior data from FLAURA showed that frontline osimertinib reduced the risk of progression or death by 54% versus erlotinib or gefitinib. In the double-blind study, the median PFS was 10.2 months for standard therapy and 18.9 months with osimertinib. The PFS benefit with osimertinib extended across all prespecified subgroups.

Additionally, the objective response rate with osimertinib was 77% compared with 69% for erlotinib and gefitinib. The median duration of response with osimertinib was 17.6 months versus 9.6 months in the comparator arm.

Based on these PFS data from FLAURA, the FDA approved osimertinib in April 2018 for use in this setting.

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

The European Commission has expanded the approval of ibrutinib to include use in combination with obinutuzumab for adult patients with previously untreated chronic lymphocytic leukemia, and also in combination with rituximab for the treatment of adult patients with Waldenström macroglobulinemia.

The expanded indications stem from a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use in June 2018.

The approval for the expanded indication in CLL is based on results of the phase III iLLUMINATE study, which showed that the combination led to a 77% reduction in the risk of progression or death versus chlorambucil plus obinutuzumab in patients with CLL or small lymphocytic lymphoma.

For the recommendation in the WM indication, the approval was based on data from the phase III iNNOVATE trial, which showed that the combination had an estimated 30-month PFS rate, which was assessed by an independent review committee, of 79% compared with 41% for those who received rituximab/placebo in patients with previously untreated and relapsed/refractory WM, at a median follow-up of 30.4 months.

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

This week, we sat down with Rafat Abonour, MD, Indiana University Health, to discuss optimizing therapy for patients with multiple myeloma.

That’s all for today.

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