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Priority Review Designation in TGCT, BLA Submitted in HER2+ Breast Cancer, and More

Gina Columbus
Published: Thursday, Feb 07, 2019



Today-

A priority review designation in tenosynovial giant cell tumor, a biologic license application submitted in HER2-positive breast cancer, a recommendation in renal cell carcinoma, encouraging findings in prostate cancer and multiple myeloma trials, and ASCO announces its Cancer Advance of the Year.

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

The FDA has granted a priority review designation to a new drug application for the CSF1R receptor inhibitor pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor.

The application is based on findings from the phase III ENLIVEN study, which demonstrated superiority in overall response rate with pexidartinib compared with placebo at 39.3% versus 0%, respectively, after 24 weeks of treatment. Responses were based on central review of magnetic resonance imaging scans.

TGCT is a nonmalignant tumor of the joint or tendon sheath, and is said to be locally aggressive and debilitating in some patients. It is also associated with severe morbidity or function limitations.

Additional results showed that no responders in the trial progressed after a median 6 months of follow-up. Tumor response was assessed by tumor volume score, which was 56% with pexidartinib and 0% with placebo.

In patients who crossed over to pexidartinib at a starting dose of 800 mg daily, the ORR and TVS were 30% and 57% at week 25, respectively.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the approval by August 3, 2019.

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

In breast cancer, a supplemental biologics license application has been submitted for ado-trastuzumab emtansine as an adjuvant therapy for patients with HER2-positive early disease who had residual disease following neoadjuvant treatment.

The sBLA is based on data from the phase III KATHERINE study, which demonstrated that T-DM1 reduced the risk of invasive disease recurrence or death by 50% versus trastuzumab in this setting. Moreover, the 3-year invasive disease-free survival rate was 88.3% with T-DM1 versus 77.0% with trastuzumab.

The iDFS benefit with T-DM1 was upheld across key patient subgroups, including operable disease at presentation, inoperable disease at presentation, negative hormone receptor status, trastuzumab as only anti-HER2 agent in the neoadjuvant setting, trastuzumab plus at least 1 anti-HER2 agent in the neoadjuvant setting, node-positive disease after neoadjuvant treatment, and node-negative disease following neoadjuvant therapy.

T-DM1 is currently approved by the FDA for the treatment of patients with metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, either alone or in combination.

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

The FDA has recommended that Aveo Oncology should not submit a new drug application for tivozanib with the preliminary overall survival data from the phase III TIVO-3 trial of patients with highly refractory, advanced or metastatic renal cell carcinoma.

The agency indicated that the preliminary data do not alleviate their concerns regarding a potential detriment in OS, which were outlined in a complete response letter issued in June 2013. Aveo Oncology, the manufacturer of the VEGF inhibitor, stated that it plans to make an NDA filing decision following the availability of additional mature OS findings.

Results showed that the median PFS was 5.6 months with tivozanib compared with 3.9 months with sorafenib, and the overall response rates were 18% versus 8%, respectively.

In the preliminary analysis of the OS endpoint, results showed a hazard ratio greater than 1, and Aveo Oncology had planned to conduct a final OS analysis in August 2019. However, due to the unexpected OS in both arms and the regulatory discussions, the company will designate the next OS analysis as an interim analysis.

Since the preliminary OS analysis in October 2018, a survival status of a subset of patients that were previously lost to follow-up, had been identified. This updated the prior hazard ratio, 1.06, to 1.12. No additional OS analyses beyond the October 4, 2018, cutoff date have been performed.

The full findings of the TIVO-3 trial are slated to be presented at the 2019 Genitourinary Cancers Symposium.

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

In prostate cancer, apalutamide in combination with androgen deprivation therapy was found to significantly improve radiographic progression-free survival and overall survival compared with placebo in patients with metastatic castration-sensitive disease, according to topline findings of the phase III TITAN trial.

Due to these preplanned data, along with a recommendation by an Independent Data Monitoring Committee, the study was unblinded by Janssen, the manufacturer of the agent. Based on the positive data, the committee recommended that patients on the placebo arm can cross over to the apalutamide group. Patients will continue to be followed for OS and long-term safety as part of the TITAN study.

Full findings will be presented at an upcoming medical meeting. Additionally, regulatory applications for apalutamide in this setting are planned to be submitted in 2019.

In February 2018, the FDA approved apalutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer, making it the first approved treatment in this setting.

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

The combination of isatuximab plus pomalidomide and low-dose dexamethasone improved progression-free survival compared with pomalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma, meeting the primary endpoint of the phase III ICARIA-MM trial.

This marks the first randomized phase III study evaluating the efficacy of adding a monoclonal antibody to pomalidomide and dexamethasone for patients with relapsed/refractory disease.

Full findings of the study will be presented at an upcoming medical meeting and will be included in regulatory submissions in 2019.

Prior results of an open-label, single-arm phase II trial showed that patients with heavily pretreated relapsed/refractory myeloma who were treated with isatuximab had a median PFS of 3.65 months and a median overall survival of 18.63 months. The overall response rate was 24.3%, including those with high-risk cytogenetics.

Additional phase III studies with isatuximab are exploring the investigational agent in combination with standard therapy for both newly diagnosed and relapsed/refractory patients.

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

ASCO has selected progress in treating rare cancers as its Advance of the Year, following major advancements made within the past year in the development of new therapies for patients with difficult-to-treat, rare malignancies.

ASCO made the announcement as part of Clinical Cancer Advances 2019: ASCO’s Annual Report on Progress Against Cancer. The annual update highlights the most impactful clinical research milestones and policy developments that have been achieved over the past year in oncology.

In a press release, ASCO President Dr Monica M. Bertagnolli said that when it comes to furthering the progress made in the cancer space as a whole, especially in rare cancers where there is a great deal of unmet need, federal investment is critical.

Therapies mentioned in the report include the FDA approvals of Lutathera for the treatment of patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors and the combination of dabrafenib and trametinib fpr patients with BRAF-mutated anaplastic thyroid carcinoma, as well as promising findings with the TKI sorafenib in patients with desmoid tumors, trastuzumab in patients with HER2-positive uterine serous carcinoma, and the CSF1R inhibitor pexidartinib for those with tenosynovial giant cell tumor.

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

This week, we sat down with Dr Stephen Ansell, of the Mayo Clinic, to discuss treating patients with CD30-positive peripheral T-cell lymphoma.

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 in tenosynovial giant cell tumor, a biologic license application submitted in HER2-positive breast cancer, a recommendation in renal cell carcinoma, encouraging findings in prostate cancer and multiple myeloma trials, and ASCO announces its Cancer Advance of the Year.

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

The FDA has granted a priority review designation to a new drug application for the CSF1R receptor inhibitor pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor.

The application is based on findings from the phase III ENLIVEN study, which demonstrated superiority in overall response rate with pexidartinib compared with placebo at 39.3% versus 0%, respectively, after 24 weeks of treatment. Responses were based on central review of magnetic resonance imaging scans.

TGCT is a nonmalignant tumor of the joint or tendon sheath, and is said to be locally aggressive and debilitating in some patients. It is also associated with severe morbidity or function limitations.

Additional results showed that no responders in the trial progressed after a median 6 months of follow-up. Tumor response was assessed by tumor volume score, which was 56% with pexidartinib and 0% with placebo.

In patients who crossed over to pexidartinib at a starting dose of 800 mg daily, the ORR and TVS were 30% and 57% at week 25, respectively.

Under the Prescription Drug User Fee Act, the FDA is scheduled to make a decision on the approval by August 3, 2019.

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

In breast cancer, a supplemental biologics license application has been submitted for ado-trastuzumab emtansine as an adjuvant therapy for patients with HER2-positive early disease who had residual disease following neoadjuvant treatment.

The sBLA is based on data from the phase III KATHERINE study, which demonstrated that T-DM1 reduced the risk of invasive disease recurrence or death by 50% versus trastuzumab in this setting. Moreover, the 3-year invasive disease-free survival rate was 88.3% with T-DM1 versus 77.0% with trastuzumab.

The iDFS benefit with T-DM1 was upheld across key patient subgroups, including operable disease at presentation, inoperable disease at presentation, negative hormone receptor status, trastuzumab as only anti-HER2 agent in the neoadjuvant setting, trastuzumab plus at least 1 anti-HER2 agent in the neoadjuvant setting, node-positive disease after neoadjuvant treatment, and node-negative disease following neoadjuvant therapy.

T-DM1 is currently approved by the FDA for the treatment of patients with metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane, either alone or in combination.

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

The FDA has recommended that Aveo Oncology should not submit a new drug application for tivozanib with the preliminary overall survival data from the phase III TIVO-3 trial of patients with highly refractory, advanced or metastatic renal cell carcinoma.

The agency indicated that the preliminary data do not alleviate their concerns regarding a potential detriment in OS, which were outlined in a complete response letter issued in June 2013. Aveo Oncology, the manufacturer of the VEGF inhibitor, stated that it plans to make an NDA filing decision following the availability of additional mature OS findings.

Results showed that the median PFS was 5.6 months with tivozanib compared with 3.9 months with sorafenib, and the overall response rates were 18% versus 8%, respectively.

In the preliminary analysis of the OS endpoint, results showed a hazard ratio greater than 1, and Aveo Oncology had planned to conduct a final OS analysis in August 2019. However, due to the unexpected OS in both arms and the regulatory discussions, the company will designate the next OS analysis as an interim analysis.

Since the preliminary OS analysis in October 2018, a survival status of a subset of patients that were previously lost to follow-up, had been identified. This updated the prior hazard ratio, 1.06, to 1.12. No additional OS analyses beyond the October 4, 2018, cutoff date have been performed.

The full findings of the TIVO-3 trial are slated to be presented at the 2019 Genitourinary Cancers Symposium.

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

In prostate cancer, apalutamide in combination with androgen deprivation therapy was found to significantly improve radiographic progression-free survival and overall survival compared with placebo in patients with metastatic castration-sensitive disease, according to topline findings of the phase III TITAN trial.

Due to these preplanned data, along with a recommendation by an Independent Data Monitoring Committee, the study was unblinded by Janssen, the manufacturer of the agent. Based on the positive data, the committee recommended that patients on the placebo arm can cross over to the apalutamide group. Patients will continue to be followed for OS and long-term safety as part of the TITAN study.

Full findings will be presented at an upcoming medical meeting. Additionally, regulatory applications for apalutamide in this setting are planned to be submitted in 2019.

In February 2018, the FDA approved apalutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer, making it the first approved treatment in this setting.

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

The combination of isatuximab plus pomalidomide and low-dose dexamethasone improved progression-free survival compared with pomalidomide and dexamethasone alone in patients with relapsed/refractory multiple myeloma, meeting the primary endpoint of the phase III ICARIA-MM trial.

This marks the first randomized phase III study evaluating the efficacy of adding a monoclonal antibody to pomalidomide and dexamethasone for patients with relapsed/refractory disease.

Full findings of the study will be presented at an upcoming medical meeting and will be included in regulatory submissions in 2019.

Prior results of an open-label, single-arm phase II trial showed that patients with heavily pretreated relapsed/refractory myeloma who were treated with isatuximab had a median PFS of 3.65 months and a median overall survival of 18.63 months. The overall response rate was 24.3%, including those with high-risk cytogenetics.

Additional phase III studies with isatuximab are exploring the investigational agent in combination with standard therapy for both newly diagnosed and relapsed/refractory patients.

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

ASCO has selected progress in treating rare cancers as its Advance of the Year, following major advancements made within the past year in the development of new therapies for patients with difficult-to-treat, rare malignancies.

ASCO made the announcement as part of Clinical Cancer Advances 2019: ASCO’s Annual Report on Progress Against Cancer. The annual update highlights the most impactful clinical research milestones and policy developments that have been achieved over the past year in oncology.

In a press release, ASCO President Dr Monica M. Bertagnolli said that when it comes to furthering the progress made in the cancer space as a whole, especially in rare cancers where there is a great deal of unmet need, federal investment is critical.

Therapies mentioned in the report include the FDA approvals of Lutathera for the treatment of patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors and the combination of dabrafenib and trametinib fpr patients with BRAF-mutated anaplastic thyroid carcinoma, as well as promising findings with the TKI sorafenib in patients with desmoid tumors, trastuzumab in patients with HER2-positive uterine serous carcinoma, and the CSF1R inhibitor pexidartinib for those with tenosynovial giant cell tumor.

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

This week, we sat down with Dr Stephen Ansell, of the Mayo Clinic, to discuss treating patients with CD30-positive peripheral T-cell lymphoma.

That’s all for today. Thank you for watching OncLive News Network! I’m Gina Columbus.
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