Mosunetuzumab/Polatuzumab Vedotin Triples PFS in LBCL

Findings showed a tripled PFS in the experimental regimen vs R-GEMOx.

The combination of mosunetuzumab-axgb (Lunsumio) with polatuzumab vedotin-piiq (Polivy) significantly decreased the risk of disease progression or death, with a tripled median progression-free survival (PFS) vs rituzimab (Rituxan) plus gemcitabine and oxaliplatin (R-GemOx) in patients with transplant-ineligible, relapsed or refractory large B-cell lymphoma (LBCL), per data from an encore presentation of the phase 3 SUNMO trial (NCT05171647) at the 2025 SOHO Annual Meeting.

Findings presented initially at the 2025 ICML Annual Meeting demonstrated that the median PFS was 11.5 months (95% CI, 5.6-17.6) with Mosun-Pola (n = 138) vs 3.8 months (95% CI, 2.9-4.1) with R-GemOx (n = 70; HR, 0.41; 95% CI, 0.28-0.61; P < .0001). PFS also favored Mosun-Pola in clinically relevant subgroups, irrespective of status to first prior therapy (relapsed: HR, 0.35; 95% CI, 0.18-0.70; refractory: HR, 0.46; 95% CI, 0.29-0.72), last prior therapy (relapsed: HR, 0.37; 95% CI, 0.16-0.88; refractory: HR, 0.39; 95% CI, 0.26-0.60), and in second- (HR, 0.38; 95% CI, 0.22-0.67) and third-line (HR, 0.49; 95% CI, 0.29-0.82) cohorts.

“SUNMO is the first positive phase 3 trial without conventional chemotherapy,” Adam J. Olszewski, MD, presenting study author and associate professor of medicine at The Warren Alpert Medical School of Brown University in Providence, Rhode Island, said during the presentation. “Mosunetuzumab plus polatuzumab vedotin is a fixed-duration outpatient regimen that combines a bispecific antibody with an antibody-drug conjugate [ADC], which provided clinically meaningful and statistically significant improvements in PFS and response in patients with transplant-ineligible, relapsed/refractory LBCL.”

What Served as the Basis for the Global, Randomized Phase 3 SUNMO Trial?

Patients with relapsed/refractory LBCL who cannot receive curative-intent treatments including CAR T-cell therapy and autologous stem cell transplant (ASCT) have poor prognosis, and the toxicities associated with alternative options such as T-cell–directed therapies can be prohibitive.¹

Mosunetuzumab is a CD20- and CD3-directed T-cell–engaging bispecific antibody, and polatuzumab vedotin is a CD79b-directed ADC––in combination, the two agents have shown lasting responses and tolerable safety profile.

Based on these data, the National Comprehensive Cancer Network’s (NCCN) Clinical Practice Guidelines in Oncology list Mosun-Pola as category 2A recommendations for the second-line treatment of patients with diffuse large B-cell lymphoma (DLBCL) who are not candidates for CAR T-cell therapy or transplant.³

How Was the SUNMO Trial Designed to Determine the Activity of Mosun-Pola?

Eligible patients included those with relapsed/refractory LBCL who had received at least 1 prior line of therapy and were ineligible for ASCT.¹ A diagnosis of LBCL was inclusive of DLBCL not otherwise specified, transformed follicular lymphoma, high-grade B-cell lymphoma, and grade 3B follicular lymphoma.

Baseline characteristics were largely evenly distributed, Olszewski said. Most patients in both arms were under the age of 65 years (57.6%), male (59.7%), and either White (49.3%) or Asian (38.9%). Most patients also had an ECOG performance status of 0 (53.6%), DLBCL (78.1%), and Ann Arbor stage III/IV disease (77.7%). Most patients did not have transformed follicular lymphoma (89.3%) or bulky disease greater than 10 cm (86.3%). With respect to therapy, patients had received a median of 2 prior lines; 56.5% received 2 or more prior lines. Patients were also predominantly primary refractory (58.6%) and refractory to their last prior therapy (69.5%).

Patients were randomly assigned 1:1 to outpatient therapy with subcutaneous mosunetuzumab on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2 through 8, plus intravenous (IV) polatuzumab vedotin every 3 weeks for 6 cycles; or IV R-GemOx on day 1 for 8 cycles. Cycles were 21 days in the investigational arm and 14 days in the control arm. Cycles were only extended to 21 days in the control arm if hematologic toxicity was present. Tumor assessments were performed at weeks 8, 16, 24, 39, and 130.

The dual primary end points were objective response rate (ORR) and PFS, both by independent review committee (IRC) assessment. Overall survival (OS) served as a key secondary end point, in addition to the incidence, nature, and severity of adverse effects.

The study was initiated in April 2022, and two years later the prespecified interim analysis of ORR by IRC was performed in the first 178 patients who had been randomized. By August 2024, 208 of the planned 222 patients had enrolled, completing the study’s accrual. The primary analysis for IRC-assessed PFS and interim OS analysis was conducted in February 2025 with a median follow-up of 23.2 months. The final OS analysis will be performed when enough OS events have occurred to provide 80% power.

What Other Data Were Presented Around Mosun-Pola’s Activity in LBCL?

Additional efficacy findings from the primary analysis illustrated that the ORR was 70.3% (95% CI, 61.9%-77.8%) with Mosun-Pola vs 40.0% (95% CI, 28.5%-52.4%) with R-GemOx (delta, 30.3%; 95% CI, 15.7%-44.9%; P < .0001). The partial response (PR) and complete response (CR) rates were also higher in the Mosun-Pola arm, at 18.8% and 51.4%, respectively, vs 15.7% and 24.3% in the R-GemOx arm.

Earlier, in the interim analysis, the ORR had been 69.7% (95% CI, 60.7%-77.8%) in the Mosun-Pola arm vs 44.1% (95% CI, 31.2%-57.6%) in the R-GemOx arm (delta, 25.7%; 95% CI, 9.6%-41.8%; P = .0008).

The CRs also proved durable. By 1 year, 72.6% (95% CI, 61.4%-83.8%) of patients in the Mosun-Pola arm remained in CR (n = 71) vs 44.1% (95% CI, 13.2%-74.9%) of those (n = 17) in the R-GemOx arm.

Interim findings from the survival analysis indicated that OS numerically favored Mosun-Pola vs R-GemOx, with median times of 18.7 months (95% CI, 14.1-not evaluable [NE]) and 13.6 months (95% CI, 9.9-NE), respectively (HR, 0.80; 95% CI, 0.54-1.20; P = .2835).

The median number of treatment cycles in the Mosun-Pola and R-GemOx arms was 8.0 (range, 1-8) and 5.0 (range, 1-8), respectively. Treatment-related adverse effects (TRAEs) occurred in 93.3% and 89.1% of patients in the respective arms; serious TRAEs occurred in 24.4% and 20.3%, respectively. Grade 3 or 4 TRAEs were reported in 52.6% and 51.6% of patients in the Mosun-Pola and R-GemOx arms, respectively; grade 5 TRAEs occurred in 2 patients in both arms. Three patients discontinued therapy in both arms because of an AE.

Does the Safety Profile of Mosun-Pola Stack Up Against Expectations?

With respect to safety, adverse effects (AEs) that occurred at least 5% more frequently in the Mosun-Pola arm (n = 135) included injection site reaction, cytokine release syndrome (CRS), skin exfoliation, COVID-19, urinary tract infection, cough, headache, arthralgia, maculopapular rash, tumor flare, and herpes zoster. AEs that were more common in the R-GemOx arm (n = 64) included thrombocytopenia, neutropenia, anemia, nausea, diarrhea, peripheral neuropathy, infusion-related reaction, vomiting, decreased white blood cell counts, peripheral sensory neuropathy, hyponatremia, infusion site extravasation, and hypoesthesia.

CRS was infrequent, early, and low grade, Olszewski said, occurring in 25.9% of patients. Grade 1, 2, and 3 CRS occurred at rates of 21.5%, 3.7%, and 0.7%, respectively, with serious cases occurring in 5.2%. The median time to onset was 3 days (range, 1-6) and the median duration was 3 days (range, 1-11). Tocilizumab (Actemra) was used for management in 4.4% of cases, whereas corticosteroids were opted for in 3.7% of cases.

Other AEs of interest in the Mosun-Pola and R-GemOx arms, respectively, included injection site reaction (52.6%; N/A), immune effector cell–associated neurotoxicity syndrome (0%; N/A), peripheral neuropathy (24.4%; 42.2%), tumor flare (6.7%; 0%), pneumonitis/interstitial lung disease (5.2%; 0%), hemophagocytic lymphohistiocytosis (0%; 0%), tumor lysis syndrome (0.7%; 0%), infections (51.1%; 31.3%), serious infections (16.3%; 14.1%), neutropenia (45.9%; 54.7%), and febrile neutropenia (2.2%; 3.1%).

“Mosunetuzumab plus polatuzumab vedotin has the lowest CRS incidence and severity among T-cell–directed therapies to date. With 96% of patients not having significant CRS, mosunetuzumab plus polatuzumab vedotin may expand patient access to a highly effective therapy and allow for broad outpatient usage at more treatment centers,” Olszewski concluded.

References

1. Westin J, Zhang H, Kim W, et al. Mosunetuzumab plus polatuzumab vedotin is superior to R-GemOx in transplant-ineligible patients with R/R LBCL: primary results of the phase III SUNMO trial. Presented at: 2025 SOHO Annual Meeting; September 3-6, 2025; Houston, TX. Abstract ABCL-1492.
2. Westin J, Zhang H, Kim W, et al. Mosunetuzumab plus polatuzumab vedotin is superior to R-GemOx in transplant-ineligible patients with R/R LBCL: primary results of the phase III SUNMO trial. Presented at: 2025 ICML Annual Meeting; June 17-21, 2025; Lugano, CH. Abstract LBA3.
3. NCCN. Clinical Practice Guidelines in Oncology. B-Cell lymphomas, version 3.2025. Accessed September 6, 2025. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf