Roche has published early clinical data on its bispecific antibody in heavily pretreated patients with metastatic colorectal cancer (mCRC). The readout hints that the T cell-activating antibody may improve outcomes in this hard-to-treat population when given as a monotherapy and in combination with anti-PD-L1 drug Tecentriq.
Investigators are testing the carcinoembryonic antigen (CEA)-targeting antibody in two early trials. In the monotherapy study, Roche has gathered data on the effect of 60-mg or larger doses of the bispecific drug in 31 mCRC patients with CEA-positive solid tumors. Of these patients, 39% had stable disease and 6% had a partial response after treatment.
The figures from the smaller number of patients to receive the bispecific and Tecentriq suggest the two drugs may complement each other. Of the 11 microsatellite-stable mCRC patients to receive a dose of the bispecific big enough to induce tumor lesion inflammation—80 mg or 160 mg—seven had stable disease and two experienced a partial response.
While the data feature a small proportion of partial responses and no complete responses, in the context of the patient population they represent encouraging findings. To join the study, patients must have either progressed after receiving standard of care or be intolerant of or nonamenable to such routine treatment. The five-year survival rate for patients with metastatic colorectal cancer is currently just above 10%.
In terms of safety, 40-mg and greater doses of the bispecific were associated with grade 3 or higher adverse events in close to 40% of patients in both the monotherapy and combination trials. Diarrhea and infusion-related reactions were the most common of such events. In the monotherapy trial, 8% of participants who received upward of 40 mg of the bispecific experienced dose-limiting toxicities. One patient died of respiratory failure after receiving a 600-mg dose.
Roche sees the data as suggesting further development of the bispecific is warranted, both in combination with Tecentriq and other drugs. The bispecific is designed to bind to CD3 receptors on T cells with one arm while also connecting to CEA on tumor cells with two arms. This mechanism is intended to bring T cells close to tumors, putting them in a position to start taking out the cancer.
Roche published data from the phase 1 trial ahead of the presentation of an abstract at the ASCO Annual Meeting 2017.