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FDA Approval in NSCLC, Priority Review Designation in SCLC, CRL to Biosimilar, and More

Gina Columbus
Published: Friday, Apr 27, 2018



Today-

An FDA approval in non—small cell lung cancer, a priority review designation in lung cancer, a complete response letter for a trastuzumab biosimilar, halted enrollment on a EZH2 inhibitor trial, and disappointing findings in trials of kidney cancer and urothelial carcinoma.

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

The FDA has approved osimertinib as a first-line treatment for patients with non–small cell lung cancer whose tumors harbor EGFR mutations, specifically exon 19 deletions or exon 21 L858R substitution mutations.

The approval of the third-generation irreversible EGFR tyrosine kinase inhibitor is based on the pivotal results of the phase III FLAURA study, in which frontline osimertinib reduced the risk of progression or death by 54% versus standard therapy with erlotinib or gefitinib. In the double-blind study, the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib.

The PFS benefit with osimertinib extended across all prespecified subgroups. In patients with brain metastases, the median PFS with osimertinib was 15.2 months compared with 9.6 months with standard therapy.

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

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Also in non–small cell lung cancer, the FDA has granted a priority review designation to a supplemental biologics license application for nivolumab for the treatment of patients with small cell lung cancer with disease progression following 2 or more lines of therapy.

The application is based on data from the phase I/II CheckMate-032 trial, in which single-agent nivolumab led to a median overall survival of 4.4 months and a 1-year OS rate of 33% in patients with progressive SCLC following more than 1 prior line of therapy.

Under the priority review, the FDA is scheduled to make its decision by August 16, 2018.

The open-label phase I/II CheckMate-032 trial evaluated nivolumab monotherapy or the combination of nivolumab and ipilimumab at different dosing schedules in patients with advanced or metastatic solid tumors, including SCLC.

The median OS in the 3 mg nivolumab/1 mg ipilimumab group was 6.0 months and the 1-year OS rate was 35%. In the 1 mg nivolumab/3 mg ipilimumab arm, the median OS was 7.7 months and the 1-year OS was 43%.

The overall response rate in the single-agent nivolumab arm was 10% and the ORRs were 23% and 19% in the 1 mg nivolumab/3 mg ipilimumab and 3 mg nivolumab/1 mg ipilimumab arms, respectively. The median duration of response was not yet reached with single-agent nivolumab.

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The FDA has issued a complete response letter to Pfizer regarding a biologics license application for the trastuzumab biosimilar PF-05280014, citing the need for additional technical information.

Pfizer had previously reported data from the REFLECTIONS B327-02 study at the 2017 ESMO Congress, which showed that the biosimilar had achieved equivalence in objective response rate versus trastuzumab when the agents were combined with paclitaxel for the frontline treatment of patients with HER2-positive metastatic breast. Survival rates at 1 year were 56% with the biosimilar and 52% with trastuzumab, and progression-free survival rates were 88.84% versus 87.96%, respectively.

A separate trial, REFLECTIONS B327-04, was presented at the 2017 ESMO Congress, and also demonstrated clinical equivalence regarding the efficacy and safety of the Pfizer biosimilar and trastuzumab.

Trastuzumab has approved FDA indications for the treatment of patients with HER2-positive breast cancer, as well as HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

The only FDA-approved biosimilar for trastuzumab is MYL-1401O, also known under the trade name Ogivri.

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The FDA has halted enrollment on clinical trials of the EZH2 inhibitor tazemetostat in patients with various solid tumors and hematologic malignancies.

The agency placed the partial clinical hold on the tazemetostat program after Epizyme, the manufacturer of the drug, provided a safety update detailing a pediatric patient with advanced poorly differentiated chordoma enrolled in a phase I trial who developed a secondary T-cell lymphoma.

The patient had been enrolled in the study for approximately 15 months at the time of the safety update and had reached a confirmed partial response. Following the diagnosis of the secondary malignancy, the patient stopped tazemetostat and is now receiving therapy for T-cell lymphoma. According to Epizyme, this is the only incident of secondary lymphoma reported among over 750 patients who have received the agent in their clinical program.

Previously enrolled patients without disease progression can continue on study. The tazemetostat program is exploring the drug as a single agent across several tumor types, including epithelioid sarcoma, follicular lymphoma, diffuse large B-cell lymphoma, and mesothelioma. Combination trials are exploring the agent in DLBCL and non-small cell lung cancer.

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

In renal cell carcinoma, interim analysis findings of the phase III ADAPT trial revealed that the immunotherapy rocapuldencel-T is unlikely to meet any of the study’s primary endpoints in patients with metastatic disease. Based on the findings, Argos Therapeutics, the manufacturer of the agent, has ended the trial.

One of the 4 coprimary endpoints, median overall survival in the intent-to-treat population, was 28.2 months for the combination of rocapuldencel-T with standard therapy versus 31.2 months with standard therapy alone.

Two other primary endpoints that were missed at the most recent analysis were OS for patients who were alive at the previous interim analysis in February 2017, and OS among all patients with at least 12 months of follow-up data. There was insufficient data to assess the fourth coprimary endpoint of 5-year survival. Argos had recently submitted a protocol amendment for the trial to the FDA detailing these 4 coprimary endpoints.

The median survival in the control group is the longest reported to date from any study of intermediate-/poor-risk patients with metastatic RCC.

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

Results of the phase III RANGE trial showed that the combination of ramucirumab and docetaxel in patients with locally advanced or unresectable metastatic urothelial carcinoma who progressed on platinum-based chemotherapy led to a positive trend, but not a statistically significant improvement, in overall survival.

The findings come from an analysis of the secondary endpoint of OS. Previously reported data showed that the study met its primary endpoint, with an improvement in progression-free survival of 1.31 months. The combination also led to a near doubling in the objective response rate versus docetaxel alone.

At a median follow-up of 5.0 months in the intent-to-treat population, the investigator-assessed median PFS was 4.07 months with the combination therapy versus 2.76 months for patients who received docetaxel alone. By independent blinded assessment, median PFS was 4.04 months versus 2.46 months in favor of ramucirumab/docetaxel.

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

This week, we sat down with Dr Ruta Rao, of Rush University Medical Center, to discuss factors influencing adjuvant therapy use for HER2-positive breast cancer.

That’s all for today.

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

An FDA approval in non—small cell lung cancer, a priority review designation in lung cancer, a complete response letter for a trastuzumab biosimilar, halted enrollment on a EZH2 inhibitor trial, and disappointing findings in trials of kidney cancer and urothelial carcinoma.

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

The FDA has approved osimertinib as a first-line treatment for patients with non–small cell lung cancer whose tumors harbor EGFR mutations, specifically exon 19 deletions or exon 21 L858R substitution mutations.

The approval of the third-generation irreversible EGFR tyrosine kinase inhibitor is based on the pivotal results of the phase III FLAURA study, in which frontline osimertinib reduced the risk of progression or death by 54% versus standard therapy with erlotinib or gefitinib. In the double-blind study, the median progression-free survival was 10.2 months for standard therapy and 18.9 months with osimertinib.

The PFS benefit with osimertinib extended across all prespecified subgroups. In patients with brain metastases, the median PFS with osimertinib was 15.2 months compared with 9.6 months with standard therapy.

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

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

Also in non–small cell lung cancer, the FDA has granted a priority review designation to a supplemental biologics license application for nivolumab for the treatment of patients with small cell lung cancer with disease progression following 2 or more lines of therapy.

The application is based on data from the phase I/II CheckMate-032 trial, in which single-agent nivolumab led to a median overall survival of 4.4 months and a 1-year OS rate of 33% in patients with progressive SCLC following more than 1 prior line of therapy.

Under the priority review, the FDA is scheduled to make its decision by August 16, 2018.

The open-label phase I/II CheckMate-032 trial evaluated nivolumab monotherapy or the combination of nivolumab and ipilimumab at different dosing schedules in patients with advanced or metastatic solid tumors, including SCLC.

The median OS in the 3 mg nivolumab/1 mg ipilimumab group was 6.0 months and the 1-year OS rate was 35%. In the 1 mg nivolumab/3 mg ipilimumab arm, the median OS was 7.7 months and the 1-year OS was 43%.

The overall response rate in the single-agent nivolumab arm was 10% and the ORRs were 23% and 19% in the 1 mg nivolumab/3 mg ipilimumab and 3 mg nivolumab/1 mg ipilimumab arms, respectively. The median duration of response was not yet reached with single-agent nivolumab.

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

The FDA has issued a complete response letter to Pfizer regarding a biologics license application for the trastuzumab biosimilar PF-05280014, citing the need for additional technical information.

Pfizer had previously reported data from the REFLECTIONS B327-02 study at the 2017 ESMO Congress, which showed that the biosimilar had achieved equivalence in objective response rate versus trastuzumab when the agents were combined with paclitaxel for the frontline treatment of patients with HER2-positive metastatic breast. Survival rates at 1 year were 56% with the biosimilar and 52% with trastuzumab, and progression-free survival rates were 88.84% versus 87.96%, respectively.

A separate trial, REFLECTIONS B327-04, was presented at the 2017 ESMO Congress, and also demonstrated clinical equivalence regarding the efficacy and safety of the Pfizer biosimilar and trastuzumab.

Trastuzumab has approved FDA indications for the treatment of patients with HER2-positive breast cancer, as well as HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

The only FDA-approved biosimilar for trastuzumab is MYL-1401O, also known under the trade name Ogivri.

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

The FDA has halted enrollment on clinical trials of the EZH2 inhibitor tazemetostat in patients with various solid tumors and hematologic malignancies.

The agency placed the partial clinical hold on the tazemetostat program after Epizyme, the manufacturer of the drug, provided a safety update detailing a pediatric patient with advanced poorly differentiated chordoma enrolled in a phase I trial who developed a secondary T-cell lymphoma.

The patient had been enrolled in the study for approximately 15 months at the time of the safety update and had reached a confirmed partial response. Following the diagnosis of the secondary malignancy, the patient stopped tazemetostat and is now receiving therapy for T-cell lymphoma. According to Epizyme, this is the only incident of secondary lymphoma reported among over 750 patients who have received the agent in their clinical program.

Previously enrolled patients without disease progression can continue on study. The tazemetostat program is exploring the drug as a single agent across several tumor types, including epithelioid sarcoma, follicular lymphoma, diffuse large B-cell lymphoma, and mesothelioma. Combination trials are exploring the agent in DLBCL and non-small cell lung cancer.

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

In renal cell carcinoma, interim analysis findings of the phase III ADAPT trial revealed that the immunotherapy rocapuldencel-T is unlikely to meet any of the study’s primary endpoints in patients with metastatic disease. Based on the findings, Argos Therapeutics, the manufacturer of the agent, has ended the trial.

One of the 4 coprimary endpoints, median overall survival in the intent-to-treat population, was 28.2 months for the combination of rocapuldencel-T with standard therapy versus 31.2 months with standard therapy alone.

Two other primary endpoints that were missed at the most recent analysis were OS for patients who were alive at the previous interim analysis in February 2017, and OS among all patients with at least 12 months of follow-up data. There was insufficient data to assess the fourth coprimary endpoint of 5-year survival. Argos had recently submitted a protocol amendment for the trial to the FDA detailing these 4 coprimary endpoints.

The median survival in the control group is the longest reported to date from any study of intermediate-/poor-risk patients with metastatic RCC.

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

Results of the phase III RANGE trial showed that the combination of ramucirumab and docetaxel in patients with locally advanced or unresectable metastatic urothelial carcinoma who progressed on platinum-based chemotherapy led to a positive trend, but not a statistically significant improvement, in overall survival.

The findings come from an analysis of the secondary endpoint of OS. Previously reported data showed that the study met its primary endpoint, with an improvement in progression-free survival of 1.31 months. The combination also led to a near doubling in the objective response rate versus docetaxel alone.

At a median follow-up of 5.0 months in the intent-to-treat population, the investigator-assessed median PFS was 4.07 months with the combination therapy versus 2.76 months for patients who received docetaxel alone. By independent blinded assessment, median PFS was 4.04 months versus 2.46 months in favor of ramucirumab/docetaxel.

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

This week, we sat down with Dr Ruta Rao, of Rush University Medical Center, to discuss factors influencing adjuvant therapy use for HER2-positive breast cancer.

That’s all for today.

Thank you for watching OncLive News Network! I’m Gina Columbus.
 
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Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Key Questions for the Use of Immunotherapy Throughout the Disease Continuum for NSCLC in an Era of Rapid DevelopmentSep 29, 20181.5
Provider and Caregiver Connection™: Addressing Patient Concerns While Managing GlioblastomaSep 29, 20182.0
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