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fda.gov/downloads/AdvisoryCommittees/CommitteesMeeti ngMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM18 0634.pdf
8. Summary
This NDA submission is based on overall tumor response rate from a single arm
phase 2 trial. The sponsor reported an overall response rate of 27% according to
IWC (n = 29). Nine patients (8%) achieved a CR and 20 patients (18%) achieved
a PR. The median duration of response was 287 days. However, 15 of 29
(51.7%) responders had their responses adjudicated because of the
disagreement between central readers 1 and 2 of the independent imaging
review committee (IRC).
According to FDA’s evaluation based on IWC, duration of response (DOR) in 13
of the 29 responders was < 14 weeks. Sixteen of these 29 responders had
confirmatory scans after initial designation of response. Thirteen of these 16
(12% of 109 evaluable patients) had a DOR of at least 14 weeks with 6 CR (5%),
1 CRu (1%) and 6 PR (5%). Median duration of response cannot be assessed in
these 16 patients due to few events and data censoring.
FDA seeks the advice of ODAC regarding the clinical significance of the overall
response rate and duration of response as well as the benefit:risk ratio for
pralatrexate treatment in patients with relapsed or refractory PTCL.
7.3 Safety
Safety assessments were performed on 111 enrolled patients who had received at least
one dose of pralatrexate. Mucositis (70%) and thrombocytopenia (41%) were the most
common AEs. AEs were the reason for dose reductions in 31%, dose omission in 69%
and treatment withdrawal in 22% of the patients.
There were a total of 49 Serious Adverse Events (SAEs) reported and those reported in
≥ 3 patients were pyrexia (8 patients), mucosal inflammation (6 patients), febrile
neutropenia (5 patients), sepsis (5 patients, 1 septic shock), and thrombocytopenia (3
patients).
Eight deaths were reported within 30 days of their last dose of pralatrexate. Seven were
attributed to PD and 1 was due to cardiopulmonary arrest (possibly related to
pralatrexate).
