Atezolizumab with cobimetinib may yield a partial response in some patients with heavily pre-treated metastatic colorectal cancer (CRC), according to research being presented at the 2018 Gastrointestinal Cancers Symposium in San Francisco, California.
Microsatellite stability (MSS), a common feature of CRC, is linked to a poor response to PD-1/PD-L1 inhibition. MEK inhibition with cobimetinib may, however, improve the response rate to checkpoint inhibition.
For this phase 1b study (ClinicalTrials.gov Identifier: NCT01988896), researchers evaluated the safety and efficacy of atezolizumab, a PD-L1 inhibitor, with cobimetinib for patients with heavily pretreated metastatic CRC.
Of 84 enrolled patients, 66 had received at least 5 prior therapies; 29 had MSS, 8 had low MS instability, and 1 had high MS instability.
The median follow-up was 14.3 months. Seven patients had a confirmed partial response: 3 with MSS, 3 with unknown MSS status, and 1 with low MS instability. The median duration of response was 14.8 months.
Less than one-third (31%) of patients had a partial response or stable disease. The median progression-free survival was 1.9 months; median overall survival was 10 months.
Treatment-related grade 3 to 4 adverse events were noted in 37% of patients.
The authors concluded that the combination “demonstrated a tolerable safety profile and improvements in [overall survival] vs those reported with [standard of care] in heavily pretreated [patients] with [metastatic] CRC.”
Bendell JC, Bang YJ, Chee CE, et al. A phase Ib study of safety and clinical activity of atezolizumab (A) and cobimetinib (C) in patients (pts) with metastatic colorectal cancer (mCRC). Oral presentation at: 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA.