Phase III IMblaze370 Study Did Not Meet Its Primary Endpoint of Overall Survival

Evaluation of the combination of atezolizumab and cobimetinib in heavily pre-treated locally advanced or metastatic CRC

On 10 May 2018, Roche and Exelixis, Inc. announced that the phase III IMblaze370 study evaluating the combination of atezolizumab (Tecentriq®) and cobimetinib (Cotellic®) did not meet its primary endpoint of overall survival (OS) compared to regorafenib. The study evaluated the combination in patients with heavily pretreated, locally advanced or metastatic colorectal cancer (CRC) whose disease progressed or who were intolerant to at least two systemic chemotherapy regimens.

Based on pre-clinical data and phase Ib data, there was a strong scientific rationale to support the further investigation of the combination of atezolizumab and cobimetinib.

The IMblaze370 study compared regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.

The study enrolled 363 patients who were randomised (2:1:1) to receive atezolizumab plus cobimetinib, or atezolizumab, or regorafenib. Patients in the combination arm received cobimetinib on days 1 to 21 plus atezolizumab on day 1 and day 15 in a 28-day cycle, until loss of clinical benefit. Patients in the monotherapy arm received atezolizumab on day 1 of each 21-day cycle, until loss of clinical benefit. Patients in the control arm received regorafenib on days 1 to 21 in a 28-day cycle, until loss of clinical benefit.

The primary endpoint was OS. Key secondary endpoints include progression-free survival, overall response rate and duration of response.

More than 95% of patients in IMblaze370 have microsatellite stable (MSS) tumours and based on the available data, immune checkpoint inhibitors as monotherapy have not demonstrated clinically meaningful efficacy in MSS mCRC. The results from IMblaze370 were consistent with this prior monotherapy experience, showing that treatment with atezolizumab alone did not provide a meaningful clinical benefit compared to regorafenib in this patient population.

Safety for the combination of atezolizumab and cobimetinib appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination.

The IMblaze370 data will be further examined in order to better understand the results and presented at an upcoming medical meeting.

Roche has an extensive clinical trial development programme for atezolizumab, with more than 50 studies ongoing, including multiple phase III studies across lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers. This includes studies evaluating atezolizumab both alone and in combination with other medicines.

Other ongoing late-stage clinical trials of cobimetinib include IMspire150 TRILOGY, a fully enrolled study of cobimetinib, vemurafenib, and atezolizumab in previously untreated patients with BRAF V600-positive metastatic melanoma; and IMspire170, which is evaluating cobimetinib and atezolizumab in BRAF V600-wild type metastatic melanoma.