FDA ODAC Votes in Favor of Polatuzumab Vedotin in Previously Untreated DLBCL

The FDA’s Oncologic Advisory Drug Committee cast an 11-to-2 vote in favor of polatuzumab vedotin-piiq (Polivy) injection’s efficacy in combination with rituximab (Rituxan) plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) in patients with previously untreated diffuse large B-cell lymphoma.¹

“Today’s committee decision to recognize the potential of this polatuzumab combination as a first-line treatment option is important since 4 in 10 people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” Levi Garraway, MD, PhD.

The meeting was conducted to determine whether polatuzumab vedotin had an observed clinical benefit in the phase 3 POLARIX trial (NCT03274492).² A final decision on the submitted supplemental biologics license application needed to be made by April 2, 2023, the prescription drug user fee act date.³

“Today’s committee decision to recognize the potential of this polatuzumab combination as a first-line treatment option is important since 4 in 10 people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a press release.⁴

The trial enrolled 879 patients who were randomly assigned 1:1 to either the polatuzumab plus R-CHP plus vincristine placebo arm or the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus polatuzumab placebo arm.

Patients received either 1.8 mg/kg of polatuzumab intravenously (IV), and IV vincristine matching placebo or polatuzumab. The experimental arm received 375 mg/m² of rituximab, 750 mg/m² IV of cyclophosphamide, and 50 mg/m² IV of doxorubicin on day 1 with prednisone given at 100 mg/day orally on days 1 to 5 of each 21-day cycle for 6 cycles. Rituximab was administered at 375 mg/m² IV as a monotherapy during cycles 7 and 8.

In the comparator patients received placebo, 375 mg/m² of rituximab, 750 mg/m² of IV cyclophosphamide, and 50 mg/m² IV of doxorubicin plus 1.4 mg/m2 of vincristine IV on day 1 and oral prednisone at 100 mg/day on days 1 to 5 of every 21-day cycle for 6 cycles. Rituximab was be given at 375 mg/m² IV as a monotherapy during cycles 7 and 8.

The primary end point was progression-free survival, with secondary end points being complete response rate, event-free survival, progression-free survival, and overall survival.

The risk of disease progression, relapse, or death was reduced by 27% in the polatuzumab plus R-CHP arm vs the placebo arm (HR, 0.73; 95% CI, 0.57-0.95; P <.02).

In terms of safety, grade 3/4 adverse effects occurred in 57.7% of patients in the polatuzumab arm vs 57.5% in the placebo. Additionally, serious AEs occurred in 34.0% vs 30.6%, grade 5 AEs in 3.0% vs 2.3%, and AEs that led to dose reduction in 9.2% vs 13.0%, respectively.

To be included in the trial, patients needed to have been previously untreated with a CD20-positive DLBCL; have archive or freshly collected tumor tissue before enrollment; an International Prognostic Index Score of 2 to 5; and ECOG performance status of 0 to 2; and adequate hematologic function.

Patients were excluded if they had a history of allergic reaction to humanized or murine monoclonal antibodies or known sensitivity to murine products; contraindicated elements of the CHOP regimen; prior organ transplant; and active peripheral neuropathy by clinical examination that was greater than grade 1.

References

1. Oncologic Drugs Advisory Committee (ODAC) Meeting. Streamed live March 9, 2023. Accessed March 10, 2023. https://bit.ly/3J8mvyd
2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304
3. FDA accepts supplemental biologics license application for Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma. News release. Roche. August 16, 2022. Accessed March 10, 2023. https://bit.ly/3C9QELH
4. FDA advisory committee votes in favour of the clinical benefit of Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma. News release. Roche. March 9, 2023. Accessed March 10, 2023. https://bit.ly/3Leeg6K