A positive top-line readout from a phase 3 trial has emboldened Incyte to seek the FDA’s blessing for the company’s Monjuvi as a first-line treatment for diffuse large B-cell lymphoma (DLBCL).
The phase 3 frontMIND trial showed that adding Monjuvi and lenalidomide (Revlimid) on top of the traditional R-CHOP regimen significantly reduced the risk of progression or death by 25% in patients with newly diagnosed DLBCL, Incyte said Monday. R-CHOP includes rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.
The trial therefore met its primary endpoint of progression-free survival (PFS) by investigator assessment. It also met a key secondary endpoint, event-free survival (EFS), which also counts the start of new anti-lymphoma treatment as a negative event.
In its Jan. 5 press release, Incyte did not disclose the exact EFS improvement number but said the frontMIND data will be shared at a future medical meeting.
Armed with the phase 3 results, Incyte said it expects to file an application for Monjuvi in first-line DLBCL in the first half of 2026. Thanks to an accelerated approval in 2020, the Monjuvi-lenalidomide combo is currently authorized as a second-line treatment for DLBCL in the U.S., and the latest frontMIND data could serve as the confirmatory evidence to facilitate a full approval.
Incyte’s chief medical officer, Steven Stein, M.D., said in a Jan. 5 statement that the Monjuvi-lenalidomide-R-CHOP combo offers “the possibility of cures for more newly diagnosed DLBCL patients.”
But Incyte might face some challenges with the FDA—and on the commercial market if its proposed regimen is approved.
First, the 25% PFS benefit is not exactly the strongest showing for an oncology trial. Back in 2023, the FDA labeled a 27% PFS improvement “modest” for Roche’s Polivy-R-CHP combo against R-CHOP.
At that time, the FDA examined the Polivy data, including the lack of an overall survival (OS) benefit, during an advisory committee meeting. Incyte’s Jan. 5 release did not provide any information on OS, another key secondary endpoint of the frontMIND trial.
“The OS analysis will be presented with the complete analysis at a future major medical meeting,” an Incyte spokesperson told Fierce Pharma.
On the positive side for Incyte, despite concerns floated by the FDA, experts on the advisory committee backed Polivy as they were convinced by the statistically significant PFS improvement, the highly efficacious R-CHOP as the comparator, and no additional toxicity. The FDA eventually approved the Roche regimen in first-line DLBCL in 2023.
FrontMIND observed no new safety signals for the Monjuvi regimen, Incyte said Monday, without offering specifics. Previously, in the phase 1b First-Mind trial, investigators reported a toxicity profile for the seven-drug Monjuvi combo that was “similar to those expected with R-CHOP.”
Even if Monjuvi wins its FDA approval, analysts at William Blair said in a Monday note that they “remain cautious on ultimate market share” for the drug given the crowded front-line DLBCL landscape.
Besides Polivy, Roche is adding its CD20xCD3 T-cell engager Columvi on top of Polivy-R-CHP in the phase 3 Skyglo trial. AbbVie and Genmab are pairing their CD20xCD3 bispecific Epkinly with R-CHOP in the Epcore DLBCL-2 trial, which is expected to read out this year.
Still, “we believe there could be a role for Monjuvi, particularly in smaller community settings or among physicians prioritizing tolerability and ease of administration for patients who may not be suitable for Polivy- or Epkinly-based regimens,” the William Blair team said.
Based on its 27% PFS benefit, Polivy-R-CHP has achieved a 35% market share in first-line DLBCL, the William Blair analysts noted. In the first three quarters of 2025, Polivy sales jumped 40% year over year to 1.1 billion Swiss francs ($1.4 billion). Monjuvi, approved in other markets as Minjuvi, reeled in about $103 million sales during the period, up 19% over the same period 2024.
DLBCL is the most common type of non-Hodgkin lymphoma, representing 40% of all cases. According to Incyte’s numbers, about 24,000 people in the U.S. and 36,000 in Europe are diagnosed with DLBCL each year.
A CD19 antibody, Monjuvi was developed by MorphoSys, which was acquired by Novartis for about $2.9 billion in 2024. Incyte initially gained partial rights to Monjuvi through a $750 million upfront deal signed with MorphoSys in 2020. The Delaware pharma took full control of the med in tandem with Novartis’ MorphoSys buyout.