FDA Accepts sBLA for Mosunetuzumab Plus Polatuzumab Vedotin in LBCL

The FDA has accepted a supplemental biologics application (sBLA) for subcutaneous mosunetuzumab-axgb (Lunsumio VELO) in combination with polatuzumab vedotin (Polivy) for adults with relapsed or refractory large B-cell lymphoma (LBCL) who have received at least 1 prior line of systemic therapy.¹ The regulatory body is expected to make a decision by February 9, 2027, which, if approved, could offer a chemotherapy-free, outpatient-ready option in this setting.

The second-line setting is a narrow window in which delays related to referral, transplant-center coordination, or travel can affect outcomes for patients with relapsed or refractory disease. An outpatient-ready, fixed-duration option that does not require transplant eligibility could allow more patients to start effective second-line treatment closer to home, without the logistical lead time that more intensive regimens often require.

"When treating [LBCL], the second-line setting represents a critical window where we must act quickly with effective therapies," Tara M. Graff, DO, MS, director of clinical research at Mission Cancer and Blood, stated in a news release.¹ "Current advanced therapies may present complex logistical and geographical barriers for many patients. Since most patients in the US are treated in the community setting, we need more chemotherapy-free, outpatient-ready treatments, like mosunetuzumab and polatuzumab vedotin."

Supporting Data From SUNMO

The filing is supported by data from the phase 3 SUNMO trial (NCT05171647), a randomized, open-label, multicenter study comparing subcutaneous mosunetuzumab plus intravenous polatuzumab vedotin with rituximab (Rituxan) plus gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed or refractory LBCL who are ineligible for autologous stem cell transplant.² The trial's dual primary end points are progression-free survival (PFS) and objective response rate; secondary outcomes include overall survival, duration of response, complete response rate, safety, and patient-reported outcomes.

A total of 208 patients were randomly assigned 2:1 to receive mosunetuzumab plus polatuzumab vedotin (n = 138) or R-GemOx (n = 70). Primary analysis data published in the Journal of Clinical Oncology in October 2025 showed that at a median follow-up of 23.2 months, the mosunetuzumab/polatuzumab vedotin combination reduced the risk of disease progression or death by 59% compared with R-GemOx (HR, 0.41; 95% CI, 0.28-0.61; P <.0001).³ Median PFS was roughly 3 times longer with the combination, at 11.5 months (95% CI, 5.6-17.6) vs 3.8 months with R-GemOx (95% CI, 2.9-4.1).

The safety profile of the combination was consistent with the known profiles of each agent individually. Cytokine release syndrome (CRS) occurred in approximately 1 in 4 patients, with fewer than 5% experiencing grade 2 or 3 events. No new safety signals emerged with additional follow-up. Updated findings presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and the 2026 European Hematology Association (EHA) Congress showed that the PFS benefit was sustained with longer follow-up, particularly among patients treated in the second-line setting.

About Mosunetuzumab and Polatuzumab Vedotin

Mosunetuzumab is a CD20×CD3 T-cell–engaging bispecific antibody that activates and redirects a patient's T cells to target and eliminate CD20-expressing B cells. It is currently approved, in both intravenous and subcutaneous (VELO) formulations, for adults with follicular lymphoma after at least 2 prior lines of therapy.

Polatuzumab vedotin is a first-in-class anti-CD79b antibody-drug conjugate that delivers a cytotoxic payload to CD79b-expressing B cells. It is currently approved in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone for previously untreated diffuse large B-cell lymphoma or high-grade B-cell lymphoma, and with bendamustine and rituximab for diffuse large B-cell lymphoma after at least 2 prior therapies.

Additional studies of mosunetuzumab in combination regimens are ongoing, including the phase 3 CELESTIMO (NCT04712097) and MorningLyte (NCT06284122) trials in second-line-or-later and frontline follicular lymphoma, respectively.

REFERENCES

1. FDA Accepts Supplemental Biologics License Application for Genentech’s Lunsumio and Polivy Combination for People With Relapsed or Refractory Large B-Cell Lymphoma. News release. Genentech. June 18, 2026. Accessed June 18, 2026. https://tinyurl.com/2y84js7e

2. A Study Evaluating Efficacy and Safety of Mosunetuzumab in Combination With Polatuzumab Vedotin Compared to Rituximab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed or Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma (SUNMO). ClinicalTrials.gov. Updated May 7, 2026. Accessed June 18, 2026. https://clinicaltrials.gov/study/NCT05171647

3. Budde LE, Zhang H, Kim WS, et al. Mosunetuzumab plus polatuzumab vedotin in transplant-ineligible refractory/relapsed large B-cell lymphoma: Primary results of the phase III SUNMO trial. J Clin Oncol. 2025;43(36):3799-3811. doi:10.1200/JCO-25-01957