Insufficient Data: Roche's CD3/20 Bispecific Antibody Faces Setback

On May 20, Roche’s official website updated that the FDA’s Oncologic Drugs Advisory Committee (ODAC) raised two concerns regarding Roche’s CD3/CD20 bispecific antibody therapy Columvi in combination treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for stem cell transplantation:

1. First, the Phase 3 Starglo trial lacks sufficient representation of U.S. patients;
2. Second, the positive trial results appear to be driven entirely by patient populations outside the U.S. and Europe.

The committee's vote showed a lopsided result of 8:1, with the only vote in favor of Columvi coming from a patient representative.

Why Are Experts Not Convinced?

The STARGLO study enrolled 274 patients across 13 countries/regions, including the U.S., Australia, and several European nations, with the majority enrolled outside Asia. In fact, 48% of participants were from Asia (with Chinese patients accounting for 34%), while only 9% were from the U.S.

Moreover, a pre-specified subgroup analysis from the STARGLO trial showed that white patients and those enrolled in Europe or North America had less favorable survival outcomes. A reanalysis revealed an even larger disparity: in Asia, Roche’s regimen reduced the risk of death by 61%, whereas in non-Asian regions, the risk of death was 6% higher compared to the control group.

The FDA speculated that the presence of effective CAR-T therapies as later-line treatments in the U.S. and Europe might have skewed the results. Roche countered in its briefing document, stating that CAR-T therapies are accessible to only a small number of patients, mainly in large academic medical centers, and are far from adequate for patients urgently needing effective treatment.

ODAC provides independent recommendations to the FDA, though these are not binding. The FDA is currently evaluating the Columvi combination therapy for relapsed/refractory DLBCL and is expected to make a decision by July 20, 2025.

Roche also stated it believes the STARGLO results are applicable to U.S. patients, noting that the global study population closely reflects the real-world clinical characteristics of U.S. DLBCL patients. Roche will continue to work with the FDA to advance regulatory progress.

About Columvi

Columvi is a bispecific CD20-targeting CD3 T-cell engager and the world’s first bispecific antibody approved for fixed-duration treatment in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). In 2023, Columvi was approved in China as a monotherapy for adult patients with R/R DLBCL who had received at least two prior lines of systemic therapy, ushering in the “dual-antibody era” in lymphoma treatment in China.

In early May, a new indication was approved domestically for use in combination with gemcitabine and oxaliplatin (GemOx) to treat adult patients with relapsed or refractory DLBCL not otherwise specified (DLBCL NOS) who are ineligible for autologous stem cell transplant (ASCT) (2L+ DLBCL).