A new group of bispecifics targeting CD20 is on the rise in lymphoma, and first-in-class Roche is digging its trench deeper with new updates for Lunsumio and market-nearing glofitamab as potential competition from AbbVie and Regeneron draw near.
Lunsumio, or mosunetuzumab, triggered a response in 77.8% of patients with follicular lymphoma who had previously tried at least two prior therapies, and 60% of patients saw no sign of cancer. The median duration of response and duration of complete response weren’t reached at the data cutoff.
The data came from a longer, median 27-month follow-up of a phase 1/2 trial. Roche previously used an earlier evaluation of the study to win a global-first approval for Lunsumio in Europe and for an FDA application that bears a target decision date for Dec. 29.
The FDA wanted more follow-up data than their counterparts did at the European Medicines Agency, hence the later ruling, Ginna Laport, M.D., global head of lymphoma and chronic lymphocytic leukemia clinical development at Roche’s Genentech, said in an interview with Fierce Pharma. The FDA wanted additional patient survival data and to make sure no late side effects emerge over the long term, she explained.
The FDA application includes data after a median follow-up of 18.3 months, which showed an 80% tumor response rate and 60% complete response rate. By investigators' estimates, 79.5% of complete responders continued to have their tumor in check for at least two years, and 51.4% of patients would be alive without disease progression after two years.
The tale of two CD20 bispecifics
The company is also working on a subcutaneous version of mosunetuzumab for convenience and safety reasons, Laport noted. The under-the-skin formulation triggered a similar 82% response rate and a 62% complete response rate in a group of patients with previously treated follicular lymphoma, according to data shared at ASH 2022.
The subcutaneous version appears to come with better safety; investigators recorded 27% of cytokine release syndrome (CRS) cases across patients with follicular lymphoma and aggressive lymphomas, and they were all below grade 3. As for infused Lunsumio, the updated analysis of the phase 1/2 trial showed a 44.4% CRS rate, and grade 3 or above cases were reported.
Lunsumio represents the first CD20xCD3 T-cell engager approved anywhere. It works by latching onto the CD20 marker on malignant B cells and the CD3 protein on T cells to bring the killer immune cells closer to neutralize the cancerous cell.
Roche has another CD20 bispecific, glofitamab, which has arrived at the FDA and the EMA for evaluation in relapsed or refractory diffuse large B-cell lymphoma. In a group of patients with heavily pretreated LBCL, 74% of patients who had seen no sign of tumor at the end of treatment remained in complete remission after a median follow-up of 18.1 months, according to data shared at ASH 2022. One of 44 patients who had at least 12 months of post-treatment follow-up experienced disease progression.
Glofitamab’s off-treatment progression rate looks “particularly encouraging” and was “rarely observed” in this treatment-experienced patient population, the trial investigators noted in an abstract. But they also cautioned that longer follow-up is needed to confirm the durability of glofitamab’s ability to maintain cancer eradication.
Roche isn’t prioritizing either one of the two CD20 bispecifics but is directing them at different diseases, Laport said. The company is developing Lunsumio for indolent non-Hodgkin lymphoma because it offers “more outpatient flexibility,” including a relatively lower CRS rate, Laport said. Glofitamab, the more potent and less tolerable agent of the two, is being developed in aggressive lymphomas.
Upcoming competitions
The Roche products, while in the lead so far in terms of regulatory progress, could face some competition from other CD20 T-cell engagers, especially ones from Regeneron and a partnership between AbbVie and Genmab.
At ASH 2022, Regeneron reported for the first time data from a higher 160mg weekly dosing of its CD20xCD3 bispecific antibody odronextamab from the pivotal ELM-2 study. In 130 patients who had failed at least two prior lines of therapy, odronextamab shrank tumors in 49.2% of patients and cleared out signs of cancer in 30.8% after a median follow-up of 21.3 months. After investigators adopted a regimen gradually stepping up treatment dosage, no grade 3 or above CRS events occurred. But five treatment-related deaths occurred because of other conditions, including COVID, pneumonia and Pseudomonas sepsis.
For glofitamab, the Roche drug had previously shown an overall response rate of 51.6% and a complete response rate of 39.4% after following a pivotal phase 2 study for a median 12.6 months. CRS occurred in 63% of patients, including combined 3.9% of grade 3 and 4 events.
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Meanwhile, AbbVie and Genmab are testing subcutaneous epcoritamab across different lymphoma types. At ASH 2022, the pair unveiled initial early-phase results for a combination pairing epcoritamab with Rituxan and Bristol Myers Squibb’s Revlimid, or R2, in newly diagnosed follicular lymphoma. Among 29 efficacy-evaluable patients, the combo posted a 90% response rate.
Fixed-duration treatment is a key selling point that Roche thinks could differentiate its bispecifics from the others, Laport said. While other candidates are given until progression, a fixed-duration therapy gives patients longer treatment intervals and could potentially reduce the probability of long-term side effects and improve the overall patient experience, she said.
In DLBCL, Roche is waiting for an FDA decision for CD97b-targeted antibody-drug conjugate Polivy, in combination with the R-CHP regimen, in newly diagnosed patients. Roche plans to launch a phase 3 trial “in the near future” to combine glofitamab with the Polivy-R-CHP cocktail in frontline DLBCL, Laport said.
Editor's Note: The odronextamab data from Regeneron has been updated.