Tecentriq-Cotellic Combo Fails to Lengthen Survival in Advanced Colorectal Cancer

Tecentriq-Cotellic Combo Fails to Lengthen Survival in Advanced Colorectal Cancer

A combination treatment of Tecentriq (atezolizumab) and Cotellic (cobimetinib) did not extend survival of patients with advanced or difficult-to-treat colorectal cancer (CRC) compared to standard therapy, Roche’s Phase 3 clinical trial shows.

Specifically, the multi-center COTEZO IMblaze370 study (NCT02788279) compared Tecentriq and Cotellic with standard Stivarga (regorafenib) treatment in patients with locally advanced or metastatic CRC, who showed disease worsening or were intolerant to at least two systemic chemotherapy regimens. A third subset of patients received Tecentriq alone.

Patients receiving the combination took Cotellic on days 1 to 21, plus Tecentriq on day 1 and day 15, in 28-day cycles. Monotherapy with Tecentriq was given on day 1 of 21-day cycles, while Stivarga was administered on days 1 to 21 in 28-day regimens. All patients received treatment until loss of clinical benefit.

Besides overall survival, which was the main goal in the analysis, the scientists also assessed progression-free survival (the length of time during or after treatment without disease worsening), overall response rate (tumor size reduction over a given period of time), and duration of response.

The study included a total of 363 patients. As for safety results, the combination of Tecentriq and Cotellic showed a similar profile to each medication alone.

“While these results are not what we hoped for, we remain committed to applying our deep experience to develop medicines that will improve outcomes for people living with gastrointestinal cancers,” Sandra Horning, MD, Roche’s chief medical officer and Head of Global Product Development, said in a press release.

“In particular, we have a number of studies evaluating medicines in colorectal cancer that could play an important role in the treatment of people with this disease in the future.”

Tecentriq is a so-called checkpoint inhibitor, which targets the PD-L1 protein. Cancer cells use binding of their own PD-1 to immune T-cells’ PD-L1 to avoid attack. Checkpoint inhibitors are used to block this binding, which boosts anti-cancer response.

Results showed that treatment with Tecentriq alone was not superior to Stivarga. More than 95 percent of patients in IMblaze370 had microsatellite stable (MSS) tumors, one of the main types of colorectal cancer. The scientists noted that prior data also do not support the use of checkpoint inhibitors alone against MSS metastatic CRC.

Roche based the Phase 3 study on positive pre-clinical and Phase 1b results. The company will proceed with the analysis of IMblaze370 data and plans to present findings at an upcoming medical meeting. Roche is investigating the Tecentriq and Cotellic treatment in other cancer types, such as melanoma.

Besides IMblaze 370 and CRC, Roche is testing Tecentriq in several Phase 3 trials, including breast, lung, kidney, skin, ovarian, bladder, prostate, blood, liver, and head and neck cancers. These studies assess Tecentriq both alone and in combination with other medications.

Cotellic is a MEK inhibitor used with Zelboraf (vemurafenib) for the treatment of metastatic or a specific type of melanoma. Combination therapies including Cotellic also are being tested in non-small cell lung cancer.