Roche has demonstrated the power of combining two of oncology’s hottest modalities—bispecifics and antibody-drug conjugates (ADCs)—in a Lunsumio-Polivy regimen in large B-cell lymphoma (LBCL).
The combination of the CD20xCD3 bispecific Lunsumio and the CD79b-directed ADC Polivy significantly reduced the risk of progression or death by 59% versus the traditional R-GemOx regimen in patients with previously treated LBCL who are not eligible for stem cell transplant. R-GemOx includes Roche’s own Rituxan and the chemotherapies gemcitabine and oxaliplatin.
Patients in the Lunsumio-Polivy group went a median 11.5 months without disease progression versus 3.8 months for R-GemOx, according to the primary analysis of the phase 3 Sunmo study presented at the International Conference on Malignant Lymphoma.
Roche said it will submit the trial results to global health authorities, including the FDA. While Lunsumio is currently approved as an intravenous infusion to treat follicular lymphoma, the Sunmo trial uses a subcutaneous formulation of the drug. Polivy, meanwhile, received the FDA’s approval as part of a combination for certain previously untreated patients with LBCL in 2023.
The positive Sunmo readout could give Roche another shot at second-line LBCL after the regulatory prospects of its other CD20xCD3 bispecific, Columvi, were thrown into doubt in the U.S.
In its own phase 3 study, Columvi, used in tandem with GemOx, led to a 63% reduction in the risk of disease worsening or death in patients with previously treated diffuse large B-cell lymphoma (DLBCL). The median progression-free survival was 12.1 months for Columvi-GemOx and 3.3 months for control. The Columvi regimen also significantly reduced the risk of death by 41% compared with R-GemOx at the primary analysis of the Starglo trial.
Despite the positive readout, an FDA advisory committee agreed with an FDA internal analysis that the Starglo results are not applicable to a U.S. patient population. The Starglo study enrolled 48% of its total population in Asia but just 9% of patients in the U.S. In addition, an FDA subgroup analysis found a negative patient survival trend in participants from non-Asian countries.
Given the bleak feedback, the Starglo regimen looks unlikely to be approved in the U.S., even though the European Commission has cleared it in second-line DLBCL.
Overall survival data remained immature in the Sunmo trial of the Lunsumio-Polivy regimen. That metric currently numerically favored Lunsumio-Polivy, with a preliminary 20% death risk reduction. But there’s no breakdown of survival data by subgroups. The study is continuing toward its final overall survival analysis.
A statistically significant overall survival showing is not required to win an approval in second-line LBCL in the U.S. The FDA has previously approved CAR-T therapies from Gilead Sciences and Bristol Myers Squibb in the disease setting based on the event-free survival endpoint.
However, regional representation might become a sticking point for Roche with the FDA again. Sunmo enrolled 20—or about 10%—of its 208 patients in the U.S. and Canada. Latin America represents 41% of the study participation and East Asia 38%.
But in a piece of good news for Roche, the progression-free survival analysis for the small North America cohort showed a massive 87% benefit in favor of Lunsumio-Polivy.
Unlike Starglo, Sunmo also enrolled patients with high-grade B-cell lymphoma and follicular lymphoma grade 3b in addition to the 78% of individuals with DLBCL. Disease progression data favored Lunsumio-Polivy in each of the three subgroups, with DLBCL’s 62% the biggest among the three lymphoma types.
The treatment effect looked similar for patients who received just one prior line of therapy versus at least two.
In terms of toxicity, the rates of treatment-related grade 3 or 4 adverse events were similar, at 52.6% and 51.6%, for Lunsumio-Polivy and R-GemOx, respectively. And treatment-related deaths were recorded in 1.5% and 3.1% of patients in the groups, respectively.
“If approved, this off-the-shelf treatment combination of [Lunsumio] and [Polivy] could be administered over a fixed period of time, without mandatory hospitalization or traditional chemotherapy, which could provide a meaningful option for patients with relapsed or refractory LBCL,” the Sunmo study’s lead author, Jason Westin, M.D., from the MD Anderson Cancer Center, said in a statement Friday.
Between its two CD20xCD3 T-cell engagers, Roche angled Columvi toward the more aggressive DLBCL in its development plan. The Swiss pharma is also running the phase 3 Skyglo study, testing the combination of Columvi, Polivy and the R-CHP regimen in first-line DLBCL.
Meanwhile, AbbVie and Genmab are running the phase 3 Epcore NHL-2 trial for its rival CD20xCD3 bispecific Epkinly in a combination with R-CHOP in newly diagnosed DLBCL.