Roche (SIX:ROG; OTCQB:RHHBY) and partner Exelixis Inc. (NASDAQ:EXEL) said Tecentriq atezolizumab plus Cotellic cobimetinib missed the primary endpoint of improving overall survival (OS) vs. Stivarga regorafenib in the Phase III IMblaze370 trial as third-line treatment of colorectal cancer. Exelixis shed $3.13 (14%) to $18.56 on Thursday, losing more than $900 million in market cap.
Roche and its Genentech Inc. unit market Tecentriq, a humanized mAb against PD-L1. Exelixis and Genentech share rights to Cotellic, a MEK inhibitor.
IMblaze370 enrolled 363 patients with locally advanced or metastatic colorectal cancer (mCRC) whose disease had progressed or who were intolerant to at least two systemic chemotherapy regimens. The trial also included an arm evaluating Tecentriq as monotherapy. Genentech plans to present the data at an upcoming medical meeting.
The miss comes a month after Roche temporarily halted recruitment in the Phase II MODUL trial to treat mCRC following four deaths in a cohort of patients receiving Tecentriq plus Cotellic. Roche told BioCentury that MODUL continues to be on a temporary hold and the company expects to determine next steps for the trial in 2H18 (see BioCentury Extra, April 10).
Genentech is also conducting two Phase III trials of Tecentriq plus Cotellic in patients with previously untreated metastatic melanoma. The IMspire170 trial is evaluating the combo in patients with BRAF V600 wild-type disease, while the IMspire150 TRILOGY trial is studying the combo plus Zelboraf vemurafenib in patients with BRAF V600 mutation-positive disease.
Tecentriq is approved in the U.S. and EU to treat metastatic non-small cell lung cancer (NSCLC) in patients whose disease has progressed during or following platinum-containing chemotherapy, as well as for locally advanced or metastatic urothelial carcinoma.
Cotellic is approved to treat unresectable or metastatic melanoma in combination with Zelboraf in patients with the BRAF V600E or V600K mutation. Zelboraf is an oral small molecule inhibitor of the oncogenic BRAF V600E.
Stivarga, a dual acting signal transduction (DAST) inhibitor of multiple kinases from Bayer AG (Xetra:BAYN), is approved to treat mCRC, gastrointestinal stromal tumors (GIST) and hepatocellular carcinoma (HCC).