Roche and Genentech were unable to sufficiently demonstrate the benefit of using Columvi in an earlier treatment setting for DLBCL in a U.S. population, according to the FDA.
The FDA has rejected Roche and subsidiary Genentech’s proposal to use the bispecific antibody Columvi as part of a second-line treatment regimen in patients with diffuse large B cell lymphoma.
In its complete response letter, the regulator cited insufficient evidence to support the use of Columvi in this indication in the U.S. patient population, according to Roche’s news release on Friday. Columvi is approved as a third-line treatment option for diffuse large B cell lymphoma (DLBCL) under the FDA’s accelerated pathway program.
Despite Friday’s rejection, Columvi “remains under accelerated approval for people with third-line or later DLBCL,” as per the company’s news release.
Delivered intravenously, Columvi is a bispecific antibody that targets both CD20, found on the surface of B cells, and CD3, expressed by T cells. This mechanism of action allows the drug to activate cancer-killing T cells and bring them closer to the malignant B cells. In 2021, Roche and Genentech kicked off the Phase III STARGLO study, combining Columvi with gemcitabine and oxaliplatin to treat patients with relapsed or refractory DLBCL.
STARGLO formed the foundation of the Columvi application, and results showed that patients treated with the Columvi combo saw a 41% drop in the risk of death compared with those who received rituximab, gemcitabine and oxaliplatin. The Columvi-based regimen likewise hit secondary endpoints, including progression-free survival.
Despite these results, the FDA’s Oncologic Drugs Advisory Committee (ODAC) in May voted 8–1 against Columvi’s expansion, raising concerns about the applicability of the drug’s efficacy data in the U.S. In STARGLO’s intention-to-treat population, only 25 of more than 270 participants were from North America.
Ravi Madan, a “no” vote who heads Prostate Cancer Clinical Research at the National Cancer Institute, said at the time of the ODAC meeting that drug sponsors should make “deliberate decisions” to make sure that their studies “apply to the U.S. population.”
Trial demography appears to be an increasingly pressing concern at the FDA. At another ODAC meeting last week to assess GSK’s application for its antibody-drug conjugate Blenrep for multiple myeloma, committee member Daniel Spratt of Western Reserve University brought up enrollment issues. GSK’s “clinical development program enrolled almost no patients in the United States,” he said.
“This is the United States FDA, so the proposed patient population [are] the United States patients,” Spratt noted. Poor enrollment from a U.S. population “precludes any assessment of the [drug’s] benefit-risk profile in the U.S.”
Aside from STARGLO, Roche and Genentech are also testing Columvi in the Phase III SKYGLO study, which combines the bispecific with Polivy, Rituxan, cyclophosphamide, doxorubicin and prednisone for the treatment of patients with large B cell lymphoma. The companies are in discussions with the FDA to use SKYGLO as the new postmarketing requirement for Columvi, as per Friday’s release.
