Roche/Genentech halts recruiting patients in Phase II MODUL trial for Tecentriq + Cotellic for metastatic colorectal cancer after four patient deaths.

Roche announced it had temporarily halted recruiting patients to its Phase II MODUL clinical trial of Tecentriq + Cotellic (atezolizumab + cobimetinib )for metastatic colorectal cancer after four patient deaths. The patients were receiving Tecentriq (atezolizumab) in combination with Exelixis � MEK inhibitor Cotellic (cobimetinib). One death was for treatment-related cardiogenic shock. Two of the deaths were because of disease progression. The fourth patient was apparently not related to treatment. The companies have emphasized that they are only stopping recruitment to evaluate the data, not halting the trial itself.

The trial is studying combinations of drugs as maintenance treatment of first-line metastatic colorectal cancer (mCRC) in biomarker-selected populations after induction treatment with FOLFOX chemotherapy and Genentech�s Avastin (bevacizumab). The specific cohort was evaluating Tecentriq plus Cotellic for HER2-negative, microsatellite instability-high (MSI-H) patients, HER2-negative, microsatellite-stable, wild-type BRAF patients, and HER2-negative, microsatellite-stable, BRAF-mutant, K-Ras (KRAS)-mutant patients. Otherwise, no new safety issues were observed. The company also indicated that the decision to temporarily halt recruitment for this trial will not affects other clinical trials ongoing for the combination treatment, including a Phase III IMblaze370 trial as third-line treatment of mCRC. Top-line results from the IMblaze370 trial are expected before mid-year.

Comment: Tecentriq is a humanized monoclonal antibody against PD-L1. It is approved in the U.S. and Europe to treat metastatic non-small cell lung cancer (NSCLC) in patients whose disease has progressed during or after platinum-containing chemotherapy, in addition to locally advanced or metastatic urothelial carcinoma.

Comment: Genentech initiated COTEZO, a phase III pivotal trial of the combination of cobimetinib and atezolizumab in unresectable locally advanced or metastatic colorectal cancer (NCT02788279). The trial is expected to enroll 360 patients who have received at least two prior chemotherapies in the metastatic disease setting. The primary endpoint of the COTEZO trial is overall survival.