ASCO: Genentech touts bispecific data for DLBCL, calling it 'groundbreaking' for heavily pretreated patients

Patients with lymphoma often relapse, finding that their cancer is even more aggressive than before. Roche’s Genentech is hoping to offer a therapy for patients who have already been through the wringer with prior lines of treatment.

Genentech will show pivotal data from the phase 2 trial of glofitamab in diffuse large B-cell lymphoma at the 2022 American Society of Clinical Oncology (ASCO) conference in June. The data comes from 155 patients who had received at least three prior lines of therapy, according to Ginna Laport, Genentech’s vice president and global head of the lymphoma/CLL development franchise.

In a sneak peek at the presentation to come, Genentech reported that the CD20xCD3 T-cell engaging bispecific antibody led to a 39% complete response, which was the primary endpoint. The therapy also spurred an overall response, including a partial or complete response, in half the participants, the secondary goal of the trial. Most of the responses were durable and continuing at 12 months, Genentech said. The company did not say whether the main or secondary goals were met. 

As for safety, cytokine release syndrome was observed in 63% of patients, the most common adverse event. Genentech said these events were predictable, generally low grade and usually occurred at initial dosing. Just one patient discontinued glofitamab due to CRS. The rate of grade 3 CRS, which is more serious, was about 4%, while there were no grade 5 events.

Glofitamab is administered in a fixed duration, meaning patients receive a certain dose and then stop, only resuming when their disease progresses, according to Laport. It is ready to administer, whereas CAR-T cell therapies used in lymphoma (Gilead’s Yescarta, Bristol Myers Squibb’s Breyanzi, Novartis’ Kymriah and Gilead’s Tecartus) require the patient to provide their own cells.

Patients also do not require preconditioning before receiving glofitamab, which is the case with CAR-Ts, Laport noted.

“This is groundbreaking for this very highly refractory population,” she said.

As for how glofitamab compares to the standard of care in this third-line setting, Laport said historical controls put responses at about 20%, which means Genentech’s offering is “well above the historical control rate.” Other potential treatments for these advanced patients include stem cell transplants and chemotherapy.

“I can confidently say that for bispecifics compared to CAR-T cell, we leverage the patient's own immune system. We use endogenous T cells to engage and fight the cancer. The patients don't have to undergo cell collection, again they don't need a conditioning regimen,” Laport said. “It's much easier to administer than obviously a stem cell transplant, then high dose chemotherapy. So again, we think this is a huge addition to the standard of care for this specific population.”

While the ASCO data will show the third-line setting, Genentech is actively working to move glofitamab up in line. A phase 3 trial for second-line diffuse large B-cell lymphoma is currently enrolling, and another study for the first line is in the works.

Genentech has already used these data to form the basis of a regulatory filing with the European Medicines Agency. Additional submissions to the FDA and other agencies around the world are expected this year.

Laport believes these data suggest that glofitamab could be first in class for bispecific antibodies, a growing field of oncology that has captured the interest of the top pharmaceutical companies. Genentech isn’t the only Big Pharma profiling these medicines at ASCO: Johnson & Johnson has a few abstracts to present on its stable of bispecifics at the conference, as well.

Genentech also has the bispecific mosunetuzumab, which is being tested in hematological malignancies including different types of lymphoma from phases 1 through 3.

“We have really the broadest and most comprehensive bispecific antibody program in the industry,” Laport said. “Between mosunetuzumab and glofitamab, we've treated over 1,400 patients between those two assets.”