ASH: Roche bispecific delivers for hard-to-treat lymphoma patients failed by CAR-Ts

Roche rolled out new data this weekend showing mosunetuzumab can trigger complete responses in a tough group—lymphoma patients failed by CAR-Ts and other drugs. The phase 1/2b linked the bispecific antibody to durable responses in a significant minority of hard-to-treat non-Hodgkin lymphoma (NHL) patients.

For the study, unveiled at the American Society of Hematology annual meeting, investigators enrolled 270 patients who had, on average, received several prior lines of therapy. The vast majority were resistant to the last therapy they took and to an earlier anti-CD20 therapy, such as Roche’s Rituxan. A little more than 10% of the subjects had previously received a CAR-T therapy.

Mosunetuzumab, a CD20xCD3 bispecific antibody designed to turn T cells on malignant B cells, showed signs of efficacy in this population. In the subset of patients with slow-growing NHL, the trial linked mosunetuzumab to objective and complete response rates (ORR/CR) of 62.7% and 43.3%, respectively.

Both response rates were lower in the larger group of patients with aggressive NHL, coming in at 37.1% and 19.4%, respectively.

In both groups, though, the responses look to be durable. More than 80% of the slow-growing NHL patients who had a complete response were in remission up to 26 months after the initial treatment. The figure for the aggressive NHL group was a little lower at 71% with up to 16 months of follow-up.  

“When we look at other therapies that are available for patients who are like these, we would in general believe that an important therapy would have a duration of response of at least 6 months, and this is much longer than that,” Genentech Senior Vice President Nancy Valente said.

Almost 30% of patients experienced a potentially serious side effect known as cytokine release syndrome (CRS). However, the cases were typically mild, with 1% of patients suffering grade 3 CRS. Close to 4% of patients experienced some type of grade 3 neurological adverse event.

Roche also generated early evidence that mosunetuzumab works in NHL patients previously treated with CAR-T therapies. In that small subpopulation, the ORR and CR were 39% and 22%, respectively.

“The data that’s really striking is after patients receive CAR-T cell therapies and progressed, they were still able to achieve complete response with the mosunetuzumab therapy, and this is really important for these patients who are really sick," Valente said. "They have very limited treatment options and not always really great responses to the therapies they receive."

The early signs of efficacy in the CAR-T population offer a couple of encouraging points for Roche and NHL patients. Firstly, the data suggest mosunetuzumab may be able to improve outcomes in a population that currently lacks treatment options. Secondly, the findings point to the potential for mosunetuzumab to establish itself in earlier lines of therapy.

CAR-T therapies have delivered durable responses in NHL patients, but they are expensive treatments that aren’t available for use immediately, due to the need to manufacture them from the patient’s own cells. Mosunetuzumab, in contrast, is an off-the-shelf therapy. When treating a disease that can progress quickly, the ability to start treatment sooner with mosunetuzumab could be a plus.

Other drugs hope to compete with mosunetuzumab for an early spot in the treatment pathway. Regeneron has generated clinical evidence that its rival CD20xCD3 bispecific antibody, REGN1979, triggers responses in NHL patients, including in people previously treated with CAR-T therapies, while Roche itself has a twist on mosunetuzumab in early phase development.

Roche shared data on its other CD20xCD3 bispecific, code-named RG6026, at ASH. In a phase 1/1b trial that gave RG6026 with Gazyva, one of Roche’s approved CD20 drugs, to 28 NHL patients, the ORR and CR were 54% and 46%, respectively.