June 10, 2019

https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761121s000lbl.pdf.

On June 10, 2019, the Food and Drug Administration granted accelerated approval to polatuzumab vedotin-piiq (POLIVY, Genentech, Inc.), a CD79b-directed antibody-drug conjugate indicated in combination with bendamustine and a rituximab product for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least two prior therapies.

Approval was based on Study GO29365 (NCT02257567), an open-label, multicenter clinical trial that included a cohort of 80 patients with relapsed or refractory DLBCL after at least one prior regimen. Patients were randomized (1:1) to receive either polatuzumab vedotin-piiq in combination with bendamustine and a rituximab product (P+BR) or BR for six 21-day cycles. Polatuzumab vedotin-piiq, 1.8 mg/kg by intravenous infusion, was given on day 2 of cycle 1 and on day 1 of subsequent cycles.  Bendamustine (90 mg/m2 intravenously) was administered on days 2 and 3 of cycle 1 and on days 1 and 2 of subsequent cycles. A rituximab product (375 mg/m2 intravenously) was administered on day 1 of each cycle.   

Efficacy was based on complete response (CR) rate and response duration, as determined by an independent review committee. At the end of therapy, the CR rate was 40% (95% CI: 25-57%) with P+BR compared with 18% (95% CI: 7-33%) with BR alone. The best overall response rate (complete and partial responses) was 63% with P+BR compared with 25% with BR. Of the 25 patients who achieved partial or complete response to P+BR, 16 (64%) had response durations of at least six months and 12 (48%) had response durations of at least 12 months.

The most common adverse reactions with P+BR (incidence at least 20%) included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia. Serious adverse reactions occurred in 64%, most often from infection. Cytopenias were the most common reason for treatment discontinuation (18% of all patients).

The prescribing information includes warnings and precautions for peripheral neuropathy, infusion-related reactions, myelosuppression, serious and opportunistic infections, progressive multifocal leukoencephalopathy, tumor lysis syndrome, hepatotoxicity, and embryo-fetal toxicity.

The recommended dose of polatuzumab vedotin-piiq is 1.8 mg/kg as an intravenous infusion over 90 minutes every 21 days for 6 cycles in combination with bendamustine and a rituximab product. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated. Premedicate with an antihistamine and antipyretic, and administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus.

View full prescribing information for POLIVY.

This indication was granted accelerated approval based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. FDA granted this application priority review, breakthrough therapy, and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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