Phase 2 data for Roche’s lymphoma ADC doesn’t disappoint

Roche Pharma's CEO suggests that the drug could shift the standard of care.

With breakthrough designation from the FDA and priority medicine status in the EU, expectations for Roche’s antibody-drug conjugate for non-Hodgkin lymphoma polatuzumab vedotin are running pretty high. Phase 2 data presented at the American Society of Hematology (ASH) annual meeting suggests that optimism could be justified.

The study shows that adding the CD79b-targeting ADC to a regimen based on Roche’s Rituxan (rituximab) and bendamustine improved complete response rates from 15% to 40% in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the most common form of NHL, who weren’t in line for bone marrow transplant.

That was accompanied by an increase in overall survival to 11.8 months from 4.7 months with Rituxan and bendamustine alone—an impressive result as transplant-ineligible DLBCL patients typically have a very poor prognosis and the study wasn’t statistically powered to show a survival benefit.

“As many as 40% of people with diffuse large B-cell lymphoma do not respond to initial therapy or experience the return of their disease, at which point their treatment options are limited and the prognosis is poor,” said Roche chief medical officer Sandra Horning, M.D., adding that the company intends to discuss the trial results with regulators.

Roche is pressing down hard on the accelerator for polatuzumab and has already started a pivotal phase 3 trial of the drug plus a widely used chemotherapy regimen (R-CHOP) in front-line DLBCL. R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) is pretty much the standard of care for previously untreated DLBCL but doesn’t work in around 40% of patients.

Roche Pharmaceuticals CEO Daniel O’Day has previously said he sees polatuzumab “shifting the standard of care” in this indication in the same way that Gazyva (obinutuzumab) has done in chronic lymphocytic leukemia and indolent NHL.

Later today, data is being presented at ASH from a phase 1b/2 trial of polatuzumab in combination with another chemo regimen—G-CHP, which combines Gazyva with cyclophosphamide, doxorubicin, and prednisone—showing a 91% overall response rate with 81% going into complete remission.

The data is also good news for Seattle Genetics, which developed the linker technology used in the ADC and licensed it to Roche’s Genentech unit back in 2002. Seattle has never disclosed the terms of that deal but has confirmed it includes fees, milestones and low- to mid-single-digit royalties on sales.