Despite a recent failure as a second-line monotherapy in diffuse B-cell lymphoma (DLBLC), a positive phase 3 combination trial for AbbVie and Genmab’s Epkinly has renewed confidence ahead of its high-stakes first-line readout.
Epkinly, used together with lenalidomide (Revlimid), significantly reduced the risk of progression or death by 60% compared with the R-GemOx regimen in the phase 3 Epcore DLBCL-4 trial, which has therefore met its primary endpoint, AbbVie and Genmab announced Monday.
Patients enrolled in the trial had DLBCL following at least one prior line of therapy. R-GemOx is a combination of rituximab plus gemcitabine and oxaliplatin.
The 60% number is based on trial censoring rules meant for the FDA. For regulators outside the U.S., the progression-free survival (PFS) improvement was similar, at 56%.
No information on overall survival, a key secondary endpoint, was provided in a June 29 release. The safety profile of the combo was consistent with previous knowledge of the individual agents, the companies said.
For analysts at Jefferies, Leerink Partners and William Blair, the positive Epcore DLBCL-4 trial increased their optimism in the upcoming, critical Epcore DLBCL-2 trial readout in first-line DLBCL, which is expected this year for Epkinly alongside the R-CHOP regimen.
Previously, the surprise failure of the Epcore DLBCL-1 trial for Epkinly monotherapy shook some investors’ confidence in the CD20xCD3 T-cell engager in a competitive field. According to results presented this month at the European Hematology Association annual meeting, Epkinly as a single agent improved PFS by 26% over physician’s choice of either R-GemOx or a bendamustine-rituximab combo. However, Epkinly failed to show a statistically significant OS, the trial’s primary endpoint. In a phenomenon that likely disadvantaged Epkinly in the OS comparison, subsequent treatment with bispecific or cell therapy was received by 26% of patients in the control arm, versus 6% in the Epkinly arm.
The latest trial win tees up increased competition between AbbVie/Genmab and Roche. In a Tuesday note to clients, Jefferies analysts estimated that Epkinly’s second-line combo regimen represents 15% of the drug’s total market opportunity, or about $700 million in peak sales.
In second-line DLBCL, the FDA last year refused to approve Roche’s Columvi, in combination with GemOx. Even though the phase 3 Starglo trial linked the Columvi regimen to a statistically significant OS improvement, the FDA flagged an imbalance in results reported from the U.S. and Asia, which appeared to have driven the benefit.
Roche is having another go with the FDA for its other CD20xCD3 bispecific, Lunsumio. In the phase 3 Sunmo study, Lunsumio plus Roche’s antibody-drug conjugate Polivy delivered a 59% PFS benefit over R-GemOx in second- or later-line DLBCL. The FDA accepted Roche’s application earlier this month, with a decision expected by Feb. 9, 2027.
In their Tuesday note, Jefferies analysts pointed out that some physicians wish to save Polivy until later lines of therapy.
For their part, William Blair analysts argued that combining subcutaneous Epkinly with oral lenalidomide offers “a simplified regimen suitable for outpatient administration.” By comparison, Roche’s Sunmo regimen requires intravenous infusion of Polivy.