FDA News

ODAC rejects accelerated approval of rociletinib for NSCLC

An FDA panel today rejected a request for accelerated approval of rociletinib to treat patients with epidermal growth factor receptor-mutated non–small cell lung cancer.

The Oncologic Drugs Advisory Committee (ODAC) voted 12 to 1 in favor of requiring the drug’s manufacturer to complete the confirmatory phase 3 study prior to approval of rociletinib (Clovis Oncology).

Rociletinib — a targeted covalent mutant-selective inhibitor — is proposed for use in patients with NSCLC who were previously treated with EGFR–targeted therapy and who harbor the EGFR T790M mutation as detected by an FDA–approved test.

The panel discussed whether the drug’s benefits outweighed its risks.

A pooled analysis of the TIGER studies — which evaluated 500-mg, 625-mg and 750-mg doses of rociletinib — demonstrated an overall response rate of 30.2% (95% CI, 25.2-35.5) and a median duration of response of 8.9 months (95% CI, 7.2-12.9) with the drug.

Almost all patients (99.5%) in the safety portion of the pooled analysis experienced an adverse event.

Common adverse events included hyperglycemia (58%), diarrhea (55%), nausea (52%), fatigue (44%), decreased appetite (36%), QT prolongation (33%) and vomiting (30%).

Serious adverse events included hyperglycemia (9%), pneumonia (5%), pancreatitis (2%), nausea (2%), vomiting (2%) and diarrhea (2%). There were two sudden deaths, three cases of ventricular tachyarrhythmia and one case of Torsade de pointes.

Seventeen percent of patients in the 625-mg dose arm died due to an adverse event.

Fifty-one percent of patients required a dose reduction, 56% of patients had a dose interruption and 21% of patients discontinued drug use due to adverse reactions.

Prior to this meeting, FDA reviewers recommended that rociletinib carry a black box warning of increased heart risk on its label, which would also include the recommendation that clinicians monitor patients’ hearts while on treatment.

A confirmatory phase 3 study is currently ongoing to compare rociletinib vs. chemotherapy in patients with EGFR T790M–positive and –negative NSCLC with acquired TKI resistance.

The FDA, which is not obligated to follow ODAC’s recommendation, is expected to make its decision on Clovis Oncology’s accelerated approval request by June 28. If it follows the opinion of the ODAC panel, a decision will not be made until the completion of the phase 3 trial in 2019.

Despite the concerns, Clovis representatives said approval of rociletinib would provide clinicians and patients with another needed treatment option.

“Rociletinib allows patients to maintain disease control through oral therapy for longer than generally less effective, less proven or less attractive options of chemotherapy or immunotherapy,” said Ross Camidge, MD, PhD, Joyce Zeff chair in lung cancer research at the University of Colorado Cancer Center and presenter for Clovis at the ODAC meeting. “Consequently, the more options we have now, the greater the chances are that we will not have to deny patients access to safe and effective treatments, simply because one size is never going to fit all in account of the therapy arena.” – by Kristie L. Kahl

An FDA panel today rejected a request for accelerated approval of rociletinib to treat patients with epidermal growth factor receptor-mutated non–small cell lung cancer.

The Oncologic Drugs Advisory Committee (ODAC) voted 12 to 1 in favor of requiring the drug’s manufacturer to complete the confirmatory phase 3 study prior to approval of rociletinib (Clovis Oncology).

Rociletinib — a targeted covalent mutant-selective inhibitor — is proposed for use in patients with NSCLC who were previously treated with EGFR–targeted therapy and who harbor the EGFR T790M mutation as detected by an FDA–approved test.

The panel discussed whether the drug’s benefits outweighed its risks.

A pooled analysis of the TIGER studies — which evaluated 500-mg, 625-mg and 750-mg doses of rociletinib — demonstrated an overall response rate of 30.2% (95% CI, 25.2-35.5) and a median duration of response of 8.9 months (95% CI, 7.2-12.9) with the drug.

Almost all patients (99.5%) in the safety portion of the pooled analysis experienced an adverse event.

Common adverse events included hyperglycemia (58%), diarrhea (55%), nausea (52%), fatigue (44%), decreased appetite (36%), QT prolongation (33%) and vomiting (30%).

Serious adverse events included hyperglycemia (9%), pneumonia (5%), pancreatitis (2%), nausea (2%), vomiting (2%) and diarrhea (2%). There were two sudden deaths, three cases of ventricular tachyarrhythmia and one case of Torsade de pointes.

Seventeen percent of patients in the 625-mg dose arm died due to an adverse event.

Fifty-one percent of patients required a dose reduction, 56% of patients had a dose interruption and 21% of patients discontinued drug use due to adverse reactions.

Prior to this meeting, FDA reviewers recommended that rociletinib carry a black box warning of increased heart risk on its label, which would also include the recommendation that clinicians monitor patients’ hearts while on treatment.

A confirmatory phase 3 study is currently ongoing to compare rociletinib vs. chemotherapy in patients with EGFR T790M–positive and –negative NSCLC with acquired TKI resistance.

The FDA, which is not obligated to follow ODAC’s recommendation, is expected to make its decision on Clovis Oncology’s accelerated approval request by June 28. If it follows the opinion of the ODAC panel, a decision will not be made until the completion of the phase 3 trial in 2019.

Despite the concerns, Clovis representatives said approval of rociletinib would provide clinicians and patients with another needed treatment option.

“Rociletinib allows patients to maintain disease control through oral therapy for longer than generally less effective, less proven or less attractive options of chemotherapy or immunotherapy,” said Ross Camidge, MD, PhD, Joyce Zeff chair in lung cancer research at the University of Colorado Cancer Center and presenter for Clovis at the ODAC meeting. “Consequently, the more options we have now, the greater the chances are that we will not have to deny patients access to safe and effective treatments, simply because one size is never going to fit all in account of the therapy arena.” – by Kristie L. Kahl