Roche’s Lunsumio may be the first CD20xCD3 T-cell engager approved by the FDA, but intravenous administration puts the drug at a disadvantage to AbbVie and Genmab’s subcutaneously injected Epkinly. That formulation gap could be closed soon.
Roche has rolled out pivotal trial data showing an under-the-skin formulation of Lunsumio works as well as the intravenous version in previously treated follicular lymphoma.
The subcutaneous version matched up to the original IV version on both trough concentration in the blood before the next dose and total body exposure to the drug up to Day 84, according to phase 2 results presented at the American Society of Hematology 2024 annual meeting.
The geometric mean ratio between the two formulations was 1.39 for the trough concentration marker and 1.06 for the accumulative endpoint, as both of their lower bounds of the 90% confidence intervals came above the predefined margin of 0.8. With the two noninferiority showings, the trial has therefore met its two co-primary pharmacokinetic endpoints, Roche said.
Last month, Roche submitted the data to the FDA in pursuit of an approval for subcutaneous Lunsumio.
The pharmacokinetics analyses only considered patients treated with an updated subcutaneous formulation starting midway through the study. Counting all patients, the efficacy of the two Lunsumio versions looked similar to one another.
The overall response rate was 81.1% for IV Lunsumio and 76.6% for subcutaneous Lunsumio, and the complete response rates were 60% and 61.7%, respectively. The median duration of response was the same at 22.8 months. The median progression-free survival duration appeared better for subcutaneous Lunsumio, at 23.7 months, versus 17.9 months for the IV form.
Subcutaneous Lunsumio requires much less time than the IV drug to administer. While the new injection takes 30 seconds to 120 seconds, the IV therapy needs about four hours in the first cycle or two hours in following cycles.
Besides convenience, the under-the-skin version also seems to offer a safety edge. The rate of grade 3 or 4 adverse events was 48.9% for subcutaneous Lunsumio and 70% for IV, according to Roche.
When it comes to cytokine release syndrome, a side effect of interest for T-cell engagers, the rate was lower at 29.8% for subcutaneous Lunsumio, compared with 44.4% for the IV version. In the subcutaneous group, serious cases happened in 16% of patients, versus 23.3% in the IV arm.
Roche is developing the new Lunsumio formulation even as AbbVie and Genmab’s subcutaneous Epkinly entered the CD20xCD3 market in June. Now, both players are trying to move into earlier lines of treatment.
Roche’s phase 3 SUNMO trial is testing Lunsumio with the company’s antibody-drug conjugate Polivy in second-line transplant-ineligible diffuse large B-cell lymphoma (DLBCL). The phase 3 CELESTIMO study is pairing Lunsumio with lenalidomide in second-line follicular lymphoma.
Roche is a little behind with its development of a subcutaneous version of its other—and more important—CD20xCD3 bispecific called Columvi. Despite regulatory filings for Columvi in second-line DLBCL and an ongoing phase 3 trial in the first line, the drug is still in its original IV form.
By comparison, AbbVie and Genmab’s phase 3 EPCORE DLBCL-2 trial is already utilizing subcutaneous Epkinly in first-line DLBCL.
One difference in the companies’ approaches is that Roche developed its offerings in fixed durations, whereas Epkinly is given indefinitely. For their all-important first-line DLBCL trials, Roche is adding Columvi to its newer Polivy-R-CHP regimen, whereas AbbVie/Genmab is utilizing the traditional R-CHOP combo.
Looking beyond bispecifics, Roche just penned a $1.5 billion deal to acquire its partner Poseida Therapeutics along with a portfolio of off-the-shelf CAR-T candidates. Poseida’s second program in line is a dual CAR-T targeting both CD19 and CD20 to treat B-cell malignancies.
“This investment in CD19, CD20 and other settings for CAR-T, we see that complementing our bispecific portfolio,” Charlie Fuchs, M.D., head of oncology and hematology product development at Roche and Genentech, said in an interview with Fierce Pharma.
Editor's Note: The story was updated with the correct overall response rates.