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FDA Approvals in CML and Hodgkin Lymphoma, Priority Review in CRC, and More

Gina Columbus
Published: Friday, Mar 30, 2018



Today-

FDA approvals in chronic myeloid leukemia and Hodgkin lymphoma, a priority review designation in colorectal cancer, a breakthrough therapy designation in urothelial carcinoma, a rolling new drug application completed in TRK-fusion cancers, and promising phase III findings in a lung cancer trial.

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

The FDA has approved nilotinib for the first- and second-line treatment of pediatric patients aged 1 year and older with Philadelphia chromosome–positive chronic myeloid leukemia in the chronic phase.

The decision was based on a cohort of 69 pediatric patients with Ph+ CML-CP enrolled across 2 trials. Patients enrolled were either newly diagnosed or resistant/intolerant to prior treatment with a tyrosine kinase inhibitor.

Results showed that the major molecular response in newly diagnosed patients was 60.0% at 12 cycles, with 15 patients achieving MMR. The cumulative MMR in this group was 64.0% by cycle 12, and the median time to first MMR was 5.6 months.

In the resistant/intolerant group, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR. The cumulative MMR rate in this group was 47.7% by cycle 12, and the median time to first MMR was 2.8 months.

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In classical Hodgkin lymphoma, the FDA has approved brentuximab vedotin for use in combination with chemotherapy as a frontline treatment for adult patients with stage III or IV disease.

The approval of the CD30-targeted antibody-drug conjugate is based on findings from the phase III ECHELON-1 trial, which demonstrated superior progression-free survival with brentuximab vedotin plus adriamycin, vinblastine, and dacarbazine versus standard ABVD.

In the study, the brentuximab vedotin regimen reduced the risk of progression, death, or initiation of new therapy by 23% compared with ABVD. Moreover, the 2-year modified PFS rate was 82.1% with brentuximab vedotin versus 77.25% for standard chemotherapy.

The approval also converts the accelerated approval the FDA previously granted the drug for adults with systemic anaplastic large cell lymphoma after failure of at least one multiagent chemotherapy regimen to a regular approval.

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The FDA has granted a priority review to a supplemental biologics license application for the combination of nivolumab and ipilimumab for the treatment of adult patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

The application is based on results from a cohort of 119 patients treated with the immunotherapy combination in the phase II CheckMate-142 study. At a median follow-up of 13.4 months, the investigator-assessed overall response rate in the cohort was 55%, with 31% of patients having stable disease. The disease control rate for more than 12 weeks was 80%. Three-fourths of 115 evaluable patients had a reduction in tumor burden from baseline.

The 55% ORR rate included 4 complete responses and 61 partial responses. Thirty-seven patients had stable disease and 14 had progressive disease. The best overall response had not yet been determined at the cutoff for 3 patients.

By comparison, patients treated with nivolumab in the monotherapy cohort of CheckMate-142 had a 31% ORR and a 69% DCR at 13 months’ follow-up.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision by July 10, 2018.

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

In urothelial carcinoma, the FDA has granted a breakthrough designation to enfortumab vedotin for patients with locally advanced or metastatic disease who previously received immune checkpoint therapy.

The designation was granted based on interim results from a phase I dose-escalation, dose-expansion trial evaluating enfortumab vedotin monotherapy in patients with metastatic urothelial carcinoma and other solid tumors. Data from the study’s metastatic urothelial carcinoma cohort showed that the antibody-drug conjugate had a 41% overall response rate among 71 evaluable patients. The ORR at the recommended phase II dose was 53%.

Among 71 evaluable patients across the entire cohort, the ORR was 41%, including 3 complete responses and 26 partial responses.

The ongoing, pivotal phase II EV-201 trial is exploring enfortumab vedotin in this setting, and the phase I EV-103 trial is exploring the agent in combination with either pembrolizumab or atezolizumab.

Enfortumab vedotin consists of an anti–Nectin-4 monoclonal antibody attached to the microtubule-disrupting agent MMAE using proprietary linker technology from Seattle Genetics.

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

A rolling new drug application has been completed for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring an NTRK gene fusion.

Loxo, the company codeveloping the pan-TRK inhibitor with Bayer, reported that the NDA had been initiated in December 2017. The rolling submission followed a breakthrough therapy designation granted by the FDA in July 2016. Moreover, Bayer plans to file a marketing authorization application in the European Union later this year.

In results published in the New England Journal of Medicine in February 2018, larotrectinib induced an objective response rate of 75% by independent review and 80% by investigator assessment in 55 evaluable patients. Per the independent assessment, there were 7 complete responses, 34 partial responses, and 5 patients with stable disease.

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

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

In non–small cell lung cancer, treatment with the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel significantly improved overall survival versus bevacizumab and chemotherapy alone for patients with advanced nonsquamous disease, according to findings from the phase III IMpower150 trial.

The OS benefit was observed across predetermined patient subgroups, including cohorts with varying PD-L1 expression levels. The toxicity profile for the combination was consistent with previous data for the drugs as single agents, with no new safety signals.

A third arm of the trial, atezolizumab plus carboplatin and paclitaxel, did not demonstrate a significant OS improvement at the interim analysis versus bevacizumab and chemotherapy, and the study is now continuing to the final analysis. Genentech, the manufacturer of atezolizumab and bevacizumab, plans to submit the latest IMpower150 findings for presentation at an upcoming medical meeting.

Previously reported data from IMpower150 showed that the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel delayed progression or death by 38% compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC.

The atezolizumab regimen demonstrated a median progression-free survival of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy alone. The 12-month PFS rate was 37% with the atezolizumab-containing regimen and 18% with the bevacizumab/chemotherapy regimen.

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

This week, we sat down with Dr Jonathan Strosberg, of Moffitt Cancer Center, to discuss how to decide on somatostatin analog treatment in neuroendocrine tumors.

That’s all for today.

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

FDA approvals in chronic myeloid leukemia and Hodgkin lymphoma, a priority review designation in colorectal cancer, a breakthrough therapy designation in urothelial carcinoma, a rolling new drug application completed in TRK-fusion cancers, and promising phase III findings in a lung cancer trial.

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

The FDA has approved nilotinib for the first- and second-line treatment of pediatric patients aged 1 year and older with Philadelphia chromosome–positive chronic myeloid leukemia in the chronic phase.

The decision was based on a cohort of 69 pediatric patients with Ph+ CML-CP enrolled across 2 trials. Patients enrolled were either newly diagnosed or resistant/intolerant to prior treatment with a tyrosine kinase inhibitor.

Results showed that the major molecular response in newly diagnosed patients was 60.0% at 12 cycles, with 15 patients achieving MMR. The cumulative MMR in this group was 64.0% by cycle 12, and the median time to first MMR was 5.6 months.

In the resistant/intolerant group, the MMR rate was 40.9% at 12 cycles, with 18 patients being in MMR. The cumulative MMR rate in this group was 47.7% by cycle 12, and the median time to first MMR was 2.8 months.

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

In classical Hodgkin lymphoma, the FDA has approved brentuximab vedotin for use in combination with chemotherapy as a frontline treatment for adult patients with stage III or IV disease.

The approval of the CD30-targeted antibody-drug conjugate is based on findings from the phase III ECHELON-1 trial, which demonstrated superior progression-free survival with brentuximab vedotin plus adriamycin, vinblastine, and dacarbazine versus standard ABVD.

In the study, the brentuximab vedotin regimen reduced the risk of progression, death, or initiation of new therapy by 23% compared with ABVD. Moreover, the 2-year modified PFS rate was 82.1% with brentuximab vedotin versus 77.25% for standard chemotherapy.

The approval also converts the accelerated approval the FDA previously granted the drug for adults with systemic anaplastic large cell lymphoma after failure of at least one multiagent chemotherapy regimen to a regular approval.

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

The FDA has granted a priority review to a supplemental biologics license application for the combination of nivolumab and ipilimumab for the treatment of adult patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

The application is based on results from a cohort of 119 patients treated with the immunotherapy combination in the phase II CheckMate-142 study. At a median follow-up of 13.4 months, the investigator-assessed overall response rate in the cohort was 55%, with 31% of patients having stable disease. The disease control rate for more than 12 weeks was 80%. Three-fourths of 115 evaluable patients had a reduction in tumor burden from baseline.

The 55% ORR rate included 4 complete responses and 61 partial responses. Thirty-seven patients had stable disease and 14 had progressive disease. The best overall response had not yet been determined at the cutoff for 3 patients.

By comparison, patients treated with nivolumab in the monotherapy cohort of CheckMate-142 had a 31% ORR and a 69% DCR at 13 months’ follow-up.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final decision by July 10, 2018.

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

In urothelial carcinoma, the FDA has granted a breakthrough designation to enfortumab vedotin for patients with locally advanced or metastatic disease who previously received immune checkpoint therapy.

The designation was granted based on interim results from a phase I dose-escalation, dose-expansion trial evaluating enfortumab vedotin monotherapy in patients with metastatic urothelial carcinoma and other solid tumors. Data from the study’s metastatic urothelial carcinoma cohort showed that the antibody-drug conjugate had a 41% overall response rate among 71 evaluable patients. The ORR at the recommended phase II dose was 53%.

Among 71 evaluable patients across the entire cohort, the ORR was 41%, including 3 complete responses and 26 partial responses.

The ongoing, pivotal phase II EV-201 trial is exploring enfortumab vedotin in this setting, and the phase I EV-103 trial is exploring the agent in combination with either pembrolizumab or atezolizumab.

Enfortumab vedotin consists of an anti–Nectin-4 monoclonal antibody attached to the microtubule-disrupting agent MMAE using proprietary linker technology from Seattle Genetics.

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

A rolling new drug application has been completed for larotrectinib for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring an NTRK gene fusion.

Loxo, the company codeveloping the pan-TRK inhibitor with Bayer, reported that the NDA had been initiated in December 2017. The rolling submission followed a breakthrough therapy designation granted by the FDA in July 2016. Moreover, Bayer plans to file a marketing authorization application in the European Union later this year.

In results published in the New England Journal of Medicine in February 2018, larotrectinib induced an objective response rate of 75% by independent review and 80% by investigator assessment in 55 evaluable patients. Per the independent assessment, there were 7 complete responses, 34 partial responses, and 5 patients with stable disease.

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

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

In non–small cell lung cancer, treatment with the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel significantly improved overall survival versus bevacizumab and chemotherapy alone for patients with advanced nonsquamous disease, according to findings from the phase III IMpower150 trial.

The OS benefit was observed across predetermined patient subgroups, including cohorts with varying PD-L1 expression levels. The toxicity profile for the combination was consistent with previous data for the drugs as single agents, with no new safety signals.

A third arm of the trial, atezolizumab plus carboplatin and paclitaxel, did not demonstrate a significant OS improvement at the interim analysis versus bevacizumab and chemotherapy, and the study is now continuing to the final analysis. Genentech, the manufacturer of atezolizumab and bevacizumab, plans to submit the latest IMpower150 findings for presentation at an upcoming medical meeting.

Previously reported data from IMpower150 showed that the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel delayed progression or death by 38% compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous NSCLC.

The atezolizumab regimen demonstrated a median progression-free survival of 8.3 months compared with 6.8 months with bevacizumab and chemotherapy alone. The 12-month PFS rate was 37% with the atezolizumab-containing regimen and 18% with the bevacizumab/chemotherapy regimen.

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

This week, we sat down with Dr Jonathan Strosberg, of Moffitt Cancer Center, to discuss how to decide on somatostatin analog treatment in neuroendocrine tumors.

That’s all for today.

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