POLARGO: Randomized Phase III study of polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin (R-GemOx) in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

TPS8070 Background: The antibody-drug conjugate polatuzumab vedotin (pola; POLIVY) targets CD79b on B-cell malignancies. Pola plus bendamustine and rituximab (BR) has significantly improved efficacy vs BR alone in patients (pts) with R/R DLBCL. As a result, pola-BR was approved by the FDA for pts with R/R DLBCL after ≥2 prior therapies. This year, the EU granted conditional marketing authorization for pola-BR in pts with stem cell transplant (SCT)-ineligible R/R DLBCL. A range of therapies are used for R/R DLBCL; one recommended option is R-GemOx. Platinum-based chemotherapies such as oxaliplatin are a preferred salvage therapy. In the POLARGO study, the safety and efficacy of pola-R-GemOx vs R-GemOx alone will be assessed in pts with R/R DLBCL. Methods: POLARGO (MO40598; NCT04182204) is a multicenter, open-label, Phase III study, comprising a safety run-in stage (pola-R-GemOx; n=10) and a randomized controlled trial (RCT) stage (pola-R-GemOx vs R-GemOx alone; expected n=206). Pts must have histologically confirmed R/R DLBCL and ECOG PS of 0–2. Exclusion criteria include prior allogeneic SCT and/or planned autologous/allogeneic SCT, and baseline grade >1 peripheral neuropathy (PN). Pts in the RCT stage will be recruited from 80–90 sites globally. The primary endpoint of the safety run-in stage is the safety and tolerability of pola-R-GemOx (pola, 1.8mg/kg; R, 375mg/m 2 ; Gem, 1000mg/m 2 ; Ox, 100mg/m 2 ) administered in 21-day cycles, with a focus on PN. In the RCT stage, pts will be stratified by number of prior lines of therapy, outcome of last systemic therapy and age, and randomized (1:1) to receive up to eight 21-day cycles of pola-R-GemOx or R-GemOx. The RCT stage primary endpoint is overall survival. Key secondary endpoints are independent review committee-assessed complete response (CR) and objective response rate (ORR; Lugano 2014 criteria). Other secondary efficacy endpoints include investigator-assessed best overall response, CR rate and ORR. Safety and health-related quality of life during treatment will be assessed. PET-CT and CT scans will be obtained at screening, during, and after the treatment period; follow-up will continue for up to 2 years. POLARGO is currently open and recruiting. Acknowledgment: POLARGO is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance, under the direction of Prof. Haioun, Dr McMillan and Dr Hernandez, was provided by Lucinda Sinclair of Gardiner-Caldwell Communications and was funded by F. Hoffmann-La Roche Ltd. Clinical trial information: NCT04182204 .