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FDA Approvals in Breast Cancer and of a Biosimilar, NDA Submitted in CLL, and More

Gina Columbus
Published: Monday, Mar 18, 2019



Today-

FDA approvals in breast cancer and of a biosimilar, a new drug application submitted in chronic lymphocytic leukemia, encouraging findings in a lung cancer trial, a European approval in non–small cell lung cancer, and an acting commissioner announced for the FDA.

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

The FDA has granted an accelerated approval to the frontline combination of atezolizumab plus nab-paclitaxel for patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer.

The approval is based on results from the phase III IMpassion130 study, which showed that the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel reduced the risk of progression or death by 40% versus nab-paclitaxel alone in this patient population.

The primary progression-free survival analysis showed that there was a clinically meaningful median PFS of 7.4 months with atezolizumab/nab-paclitaxel and 4.8 months with chemotherapy. The 1-year PFS rates were 29% and 16% with atezolizumab/nab-paclitaxel and nab-paclitaxel, respectively.

In the intent-to-treat population, the median PFS with atezolizumab/nab-paclitaxel and nab-paclitaxel was 7.2 months and 5.5 months, respectively. Here, the 1-year PFS rates were 24% in the combination arm and 18% for those who received nab-paclitaxel.

At a 12.9-month follow-up, an interim overall survival analysis of the PD-L1–positive population showed a median OS of 25.0 months with the atezolizumab regimen versus nab-paclitaxel alone at 15.5 months. Two-year OS rates were 54% versus 37%, respectively.

In the ITT population, the P value for OS was .0840. However, OS was not formally tested in a statistical design in the PD-L1–positive subgroup but was tested in the overall study population.

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

The FDA has approved the trastuzumab biosimilar PF-05280014, known by the trade name Trazimera, for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. This is the fourth FDA approval for a trastuzumab biosimilar.

The decision was based on findings of a comprehensive data package, including results from the phase III REFLECTIONS B327-02 trial, demonstrating similar efficacy and safety outcomes between PF-05280014 and standard trastuzumab.

Results from REFLECTIONS B327-02 showed that the biosimilar met its primary endpoint for equivalent objective response rate versus trastuzumab as a frontline treatment for patients with HER2-positive metastatic breast cancer.

Additional data showed that the risk ratio achieved the equivalence margin of 0.8 to 1.25 specified in the clinical trial design. Moreover, the 1-year PFS was 56% for PF-05280014 versus 52% for trastuzumab-EU, and the 1-year OS was 88.84% versus 87.96%, respectively.

No new safety signals were reported with the biosimilar, and the safety profile was similar between arms.

The European Medicines Agency approved the biosimilar in this setting in July 2018.

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

In chronic lymphocytic leukemia, a supplemental new drug application was filed for the combination of venetoclax and obinutuzumab for the treatment of patients with previously untreated disease who also have coexisting medical conditions.

The submission is based on data from the randomized, phase III CLL14 study, in which a fixed-duration of venetoclax plus obinutuzumab demonstrated a statistically significant reduction in the risk of disease progression or death versus obinutuzumab plus chlorambucil in treatment-naïve patients with CLL and coexisting medical conditions.

Additionally, no new safety signals were reported with the combination, and the safety profile of the 2-drug regimen was consistent with that of each agent alone.

The agency is reviewing the sNDA under the Real-Time Oncology Review pilot program, which is designed to have a more efficient review process to make therapies more quickly available to patients.

Preliminary data from this study showed that after 3 cycles of treatment with venetoclax and obinutuzumab, the overall response rate was 92%. However, after 6 cycles of treatment with the combination, the ORR increased to 100%.

Full findings of the CLL14 trial will be presented at an upcoming medical meeting.

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

The combination of ramucirumab and erlotinib significantly improved progression-free survival versus placebo and erlotinib as a frontline treatment for patients with metastatic EGFR-mutant non–small cell lung cancer, meeting the primary endpoint of the phase III RELAY trial.

The safety profile was consistent with what was previously reported in clinical trials of each agent alone.

The most common grade ≥3 adverse events that occurred at a higher rate on the combination arm versus erlotinib with placebo were hypertension, dermatitis acneiform, and diarrhea.

Full findings will be presented at an upcoming medical meeting. Based on these findings, Eli Lilly and Company, the manufacturer of ramucirumab, stated that it will be submitting applications to regulatory agencies later in 2019.

In non¬–small cell lung cancer, ramucirumab is currently approved in combination with docetaxel as a treatment for patients with metastatic disease whose tumor has progressed during or following treatment with platinum-based chemotherapy.

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

In non¬–small cell lung cancer, the European Commission has approved and granted marketing authorization to the frontline combination of atezolizumab, bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic, nonsquamous disease.

For patients with EGFR or ALK molecular abnormalities, the 4-drug regimen should be indicated only after progression on appropriate targeted therapies.

The decision is based on findings from the phase III IMpower150 study, which showed that the combination of atezolizumab, bevacizumab, and chemotherapy improved overall survival versus bevacizumab plus chemotherapy alone.

Moreover, the median OS was 19.8 months with the atezolizumab regimen versus 14.9 months with bevacizumab/carboplatin/paclitaxel in the intent-to-treat population.

The decision follows a positive opinion granted by the European Medicine’s Agency Committee for Medicinal Products for Human Use for the frontline regimen in February 2019. The FDA approved the frontline regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel in this setting in December 2018.

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

National Cancer Institute director Dr. Norman (Ned) E. Sharpless, has been named acting commissioner of the FDA once Dr. Scott Gottlieb, leaves the regulatory agency in April 2019, according to an announcement by the Health and Human Services Secretary.

The news was released at a House Energy and Commerce Health Subcommittee Hearing one week after Gottlieb announced his plan to resign in early April after nearly 2 years of service.

Sharpless was sworn in as the 15th director of the NCI on October 17, 2017. Prior to the appointment, he served as the director of the University of North Carolina at Chapel Hill’s Lineberger Comprehensive Cancer Center.

During his time at UNC, Sharpless also codirected a large clinical trial referred to as UNCseq, which used next-generation sequencing of tumor DNA as a way to define optimal chemotherapy in patients with advanced cancer in real-time. He has also authored over 150 scientific papers, reviews, and book chapters.

With this move, Douglas R. Lowy, MD, prior deputy director of the NCI will now serve as acting director for the institute.

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

This week, we sat down with Dr Anna C. Pavlick, of NYU Langone’s Perlmutter Cancer Center, to discuss a phase I trial of the anti–PD-1 agent cemiplimab.

That’s all for today.

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

FDA approvals in breast cancer and of a biosimilar, a new drug application submitted in chronic lymphocytic leukemia, encouraging findings in a lung cancer trial, a European approval in non–small cell lung cancer, and an acting commissioner announced for the FDA.

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

The FDA has granted an accelerated approval to the frontline combination of atezolizumab plus nab-paclitaxel for patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer.

The approval is based on results from the phase III IMpassion130 study, which showed that the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel reduced the risk of progression or death by 40% versus nab-paclitaxel alone in this patient population.

The primary progression-free survival analysis showed that there was a clinically meaningful median PFS of 7.4 months with atezolizumab/nab-paclitaxel and 4.8 months with chemotherapy. The 1-year PFS rates were 29% and 16% with atezolizumab/nab-paclitaxel and nab-paclitaxel, respectively.

In the intent-to-treat population, the median PFS with atezolizumab/nab-paclitaxel and nab-paclitaxel was 7.2 months and 5.5 months, respectively. Here, the 1-year PFS rates were 24% in the combination arm and 18% for those who received nab-paclitaxel.

At a 12.9-month follow-up, an interim overall survival analysis of the PD-L1–positive population showed a median OS of 25.0 months with the atezolizumab regimen versus nab-paclitaxel alone at 15.5 months. Two-year OS rates were 54% versus 37%, respectively.

In the ITT population, the P value for OS was .0840. However, OS was not formally tested in a statistical design in the PD-L1–positive subgroup but was tested in the overall study population.

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

The FDA has approved the trastuzumab biosimilar PF-05280014, known by the trade name Trazimera, for the treatment of patients with HER2-overexpressing breast cancer as well as HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. This is the fourth FDA approval for a trastuzumab biosimilar.

The decision was based on findings of a comprehensive data package, including results from the phase III REFLECTIONS B327-02 trial, demonstrating similar efficacy and safety outcomes between PF-05280014 and standard trastuzumab.

Results from REFLECTIONS B327-02 showed that the biosimilar met its primary endpoint for equivalent objective response rate versus trastuzumab as a frontline treatment for patients with HER2-positive metastatic breast cancer.

Additional data showed that the risk ratio achieved the equivalence margin of 0.8 to 1.25 specified in the clinical trial design. Moreover, the 1-year PFS was 56% for PF-05280014 versus 52% for trastuzumab-EU, and the 1-year OS was 88.84% versus 87.96%, respectively.

No new safety signals were reported with the biosimilar, and the safety profile was similar between arms.

The European Medicines Agency approved the biosimilar in this setting in July 2018.

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

In chronic lymphocytic leukemia, a supplemental new drug application was filed for the combination of venetoclax and obinutuzumab for the treatment of patients with previously untreated disease who also have coexisting medical conditions.

The submission is based on data from the randomized, phase III CLL14 study, in which a fixed-duration of venetoclax plus obinutuzumab demonstrated a statistically significant reduction in the risk of disease progression or death versus obinutuzumab plus chlorambucil in treatment-naïve patients with CLL and coexisting medical conditions.

Additionally, no new safety signals were reported with the combination, and the safety profile of the 2-drug regimen was consistent with that of each agent alone.

The agency is reviewing the sNDA under the Real-Time Oncology Review pilot program, which is designed to have a more efficient review process to make therapies more quickly available to patients.

Preliminary data from this study showed that after 3 cycles of treatment with venetoclax and obinutuzumab, the overall response rate was 92%. However, after 6 cycles of treatment with the combination, the ORR increased to 100%.

Full findings of the CLL14 trial will be presented at an upcoming medical meeting.

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

The combination of ramucirumab and erlotinib significantly improved progression-free survival versus placebo and erlotinib as a frontline treatment for patients with metastatic EGFR-mutant non–small cell lung cancer, meeting the primary endpoint of the phase III RELAY trial.

The safety profile was consistent with what was previously reported in clinical trials of each agent alone.

The most common grade ≥3 adverse events that occurred at a higher rate on the combination arm versus erlotinib with placebo were hypertension, dermatitis acneiform, and diarrhea.

Full findings will be presented at an upcoming medical meeting. Based on these findings, Eli Lilly and Company, the manufacturer of ramucirumab, stated that it will be submitting applications to regulatory agencies later in 2019.

In non¬–small cell lung cancer, ramucirumab is currently approved in combination with docetaxel as a treatment for patients with metastatic disease whose tumor has progressed during or following treatment with platinum-based chemotherapy.

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

In non¬–small cell lung cancer, the European Commission has approved and granted marketing authorization to the frontline combination of atezolizumab, bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic, nonsquamous disease.

For patients with EGFR or ALK molecular abnormalities, the 4-drug regimen should be indicated only after progression on appropriate targeted therapies.

The decision is based on findings from the phase III IMpower150 study, which showed that the combination of atezolizumab, bevacizumab, and chemotherapy improved overall survival versus bevacizumab plus chemotherapy alone.

Moreover, the median OS was 19.8 months with the atezolizumab regimen versus 14.9 months with bevacizumab/carboplatin/paclitaxel in the intent-to-treat population.

The decision follows a positive opinion granted by the European Medicine’s Agency Committee for Medicinal Products for Human Use for the frontline regimen in February 2019. The FDA approved the frontline regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel in this setting in December 2018.

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

National Cancer Institute director Dr. Norman (Ned) E. Sharpless, has been named acting commissioner of the FDA once Dr. Scott Gottlieb, leaves the regulatory agency in April 2019, according to an announcement by the Health and Human Services Secretary.

The news was released at a House Energy and Commerce Health Subcommittee Hearing one week after Gottlieb announced his plan to resign in early April after nearly 2 years of service.

Sharpless was sworn in as the 15th director of the NCI on October 17, 2017. Prior to the appointment, he served as the director of the University of North Carolina at Chapel Hill’s Lineberger Comprehensive Cancer Center.

During his time at UNC, Sharpless also codirected a large clinical trial referred to as UNCseq, which used next-generation sequencing of tumor DNA as a way to define optimal chemotherapy in patients with advanced cancer in real-time. He has also authored over 150 scientific papers, reviews, and book chapters.

With this move, Douglas R. Lowy, MD, prior deputy director of the NCI will now serve as acting director for the institute.

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

This week, we sat down with Dr Anna C. Pavlick, of NYU Langone’s Perlmutter Cancer Center, to discuss a phase I trial of the anti–PD-1 agent cemiplimab.

That’s all for today.

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