US FDA has received a total of 19 reports of T-cell malignancy involving BCMA- or CD19-directed autologous CAR-T cell immunotherapies and is evaluating the need for regulatory action. Focus on lentiviral and retroviral vectors could extend to safety of other types of gene therapies.

At advisory committee meeting on Acrotech's two peripheral T-cell lymphoma drugs, FDA reviewers suggest they are more willing to seek product withdrawal for failure to conduct studies with due diligence when there are numerous available therapies.

Accelerated approval sponsors who want to demonstrate due diligence in conducting confirmatory trials should bring a comprehensive program for verifying benefit to the agency early and be proactive in communicating about challenges that could lead to delays, FDA’s oncology review staff say at an adcomm on delayed trials for Acrotech’s lymphoma drugs.

There is a greater commitment among larger, well-capitalized oncology companies to complete confirmatory trials, Oncology Center of Excellence Director Richard Pazdur says; smaller company approach of first getting accelerated approval and then using commercial proceeds to capitalize confirmatory trial is ‘unacceptable.’

Seven-year timeline for Phase III trial in first-line peripheral T-cell lymphoma is too long, advisory committee members say, also questioning study feasibility; some panelists favor Richard Pazdur’s push for a second, concurrent trial in the relapsed/refractory setting that could read out sooner.

Confirmatory trials for anti-cancer drugs should be targeted for completion no later than two to four years after accelerated approval is granted, agency says, offering various strategies and factors sponsors should consider to ensure they are conducting studies with due diligence.