POLARGO: A Randomized Phase III Study Evaluating Polatuzumab Vedotin Plus Rituximab, Gemcitabine, and Oxaliplatin in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Who Had Received One or More Previous Therapies

Introduction: The antibody-drug conjugate polatuzumab vedotin (pola) targets CD79b on B-cell malignancies. Pola in combination with bendamustine and rituximab (BR) improved complete response (CR) rate and overall survival (OS) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), compared with BR alone (CR rate: 40% vs 18%, respectively, p=0.026; median OS: 12.4 vs 4.7 months, respectively, p=0.0023; Sehn et al. ASH 2018). Based on these results, pola + BR was recently approved by the FDA for patients with R/R DLBCL after at least two prior therapies. NCCN guidelines (2019) suggest multiple second-line and subsequent treatment options for patients with R/R DLBCL; in practice, a wide range of options are used (Herrera et al. Hematol Oncol 2019). One recommended option is rituximab plus gemcitabine and oxaliplatin (R-GemOx; Mounier et al. Haematol 2013; Cazelles et al. Hematol Oncol 2019). Platinum-based chemotherapies such as oxaliplatin are a preferred salvage approach for patients with R/R DLBCL (Tilly et al. Ann Oncol 2015). The safety of pola combined with platinum-based therapies in R/R DLBCL has not yet been assessed, and both pola and platinum-based therapies are associated with neuropathy. In the POLARGO study, we will assess the safety and efficacy of pola in combination with R-GemOx, compared with R-GemOx alone, in patients with R/R DLBCL. Methods: POLARGO (MO40598) is a multicenter, open-label, Phase III study, comprising two stages: 1) a safety run-in stage evaluating pola + R-GemOx in 10 patients and 2) a randomized controlled trial (RCT) stage comparing pola + R-GemOx with R-GemOx alone in an expected 206 patients. In the RCT stage, patients will be recruited from 80─90 sites globally. Patients must have histologically confirmed R/R DLBCL, confirmed availability of archival or freshly collected tumor tissue (RCT stage), and ECOG performance status of 0-2. Relapse is defined as disease that recurs following a response lasting ≥ 6 months from completion of the last line of therapy. Refractory is defined as disease that progressed during previous therapy or stable disease for up to 6 months from completion of the last line of therapy. Patients will be excluded if they have had allogeneic stem-cell transplantation (SCT) and/or have planned autologous/allogeneic SCT. Patients with baseline peripheral neuropathy greater than grade 1 (as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events,