Approval moves Roche Columvi earlier in DLBCL treatment pathway

 A regimen based on Roche's CD20xCD3 bispecific antibody Columvi has been approved in the EU as a second-line therapy for diffuse large B-cell lymphoma (DLBCL), the first in the class that can be used at this stage in the treatment pathway.

The approval is based on the phase 3 STARGLO trial, where Columvi (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) chemotherapy achieved a 41% reduction in the risk of death compared to Roche's anti-CD20 antibody MabThera/Rituxan (rituximab) plus chemo.

The Columvi combination also met its key secondary endpoints, with a 63% reduction in the risk of disease worsening or death compared to the control treatment.

Columvi has already been given conditional approval in Europe as a third-line or later treatment option for DLBCL, and the STARGLO data should help convert that to a full approval, according to Roche. In that indication, the drug competes with AbbVie and Genmab's rival CD20xCD3 bispecific Epkinly (epcoritamab), so, moving it into the first relapse setting could hand Roche an advantage.

Specifically, the European Commission has cleared Columvi for patients whose cancer has returned after initial treatment, but who are not eligible for autologous stem cell transplant (ASCT). The US FDA is due to make a decision on the new indication by 20th July.

It also means Columvi has become an off-the-shelf alternative to CAR-T therapies for NHL like Gilead Sciences' Yescarta (axicabtagene ciloleucel), Novartis' Kymriah (tisagenlecleucel), and Bristol-Myers Squibb's Breyanzi (lisocabtagene maraleucel) in second-line DLBCL treatment, which have complex manufacturing and administration procedures and require in-clinic care.

"People with [relapsed/refractory] DLBCL not eligible for ASCT represent a challenging population, especially those with primary refractory disease or early relapse whose need for a readily accessible and effective therapy is insufficiently addressed globally," said Franck Morschhauser, a STARGLO study investigator at the University Hospital Lille.

"This new Columvi combination is immediately available if a patient's cancer returns or doesn't respond to first-line therapy, which is a welcome addition to manage DLBCL," he added.

Roche's bispecific rivals are also looking to move Epkinly further up the treatment pathway, and Epkinly is being tested as a second-line option in the phase 3 EPCORE DLBCL-1 study, comparing it as a monotherapy to investigators’ choice of chemo in patients who did not respond to or are ineligible for an ASCT, with results due next year.

Meanwhile, AbbVie and Genmab are also running the Epcore DLBCL-4 trial, which is testing Epkinly plus Bristol-Myers Squibb's Revlimid (lenalidomide) in relapsed/refractory DLBCL patients who have failed or are ineligible for autologous stem cell transplant.

Roche maintains that a key difference between Columvi and Epkinly is that its drug uses a fixed duration of treatment, while AbbVie and Genmab’s therapy needs to be administered until the disease progresses.

That may allow for time off treatment that could reduce the risk of long-term side effects, it contends. Meanwhile, AbbVie and Genmab reckon that their drug is less likely to cause side effects like cytokine release syndrome (CRS) and has an easier route of administration (subcutaneous instead of intravenous).

https://pharmaphorum.com/news/approval-moves-columvi-earlier-dlbcl-treatment-pathway