Genentech’s Tecentriq Flunks Phase III for Colorectal Cancer

Clinical Trials Failure

Genentech, a Roche company, reported that its Phase III IMblaze370 trial of Tecentriq (atezolizumab) and Cotellic (cobimetinib) for difficult-to-treat, locally advanced or metastatic colorectal cancer (CRC) did not meet its primary endpoint of overall survival (OS) compared to Bayer’s Stivarga (regorafenib).

The trial was in patients whose cancer had progressed or who did not tolerate at least two chemotherapy treatments. More than 95 percent of the patients in the study have microsatellite stable (MSS) tumors. Based on its available data, the company is saying that checkpoint inhibitors alone didn’t show meaningful efficacy in MSS mCRC. Part of the underlying theory of the trial is that by adding Cotellic, a MEK inhibitor, to the treatment regimen, it would be more effective. However, this appears to disprove that theory.

“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,” said Sandra Horning, Roche/Genentech’s chief medical officer and head of Global Product Development, in a statement. “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.”

The IMblaze370 trial is a Phase III, multi-center, open-label, three-arm, randomized study. It compares regorafenib, a standard of care treatment in this setting, to Cotellic and Tecentriq and Tecentriq alone. It enrolled 363 patients who were randomized 2:1:1.

This news comes about a month after Genentech announced it had temporarily halted recruiting patients to its Phase II MODUL clinical trial for metastatic colorectal cancer after four patient deaths. The patients were receiving Tecentriq in combination with Exelixis ’ Cotellic. One death was for treatment-related cardiogenic shock. Two of the deaths were because of disease progression. The fourth death was apparently not related to treatment. The companies emphasized that they were only stopping recruitment to evaluate the data, not halting the trial itself.

That trial is studying combinations of drugs as maintenance treatment of first-line metastatic colorectal cancer 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.

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.

Cotellic, marketed by Exelixis and Genentech, has been approved to treat unresectable or metastatic melanoma in combination with Zelboraf (vemurafenib) in patients with the BRAF V600E or V600K mutation.

Tecentriq is involved in more than 50 ongoing clinical studies, including Phase III trials in lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers. Cotellic is also being studied in combination with several investigational drugs, including Tecentriq, in several cancers including non-small cell lung cancer, melanoma and colorectal cancer.

In a statement, Michael Morrissey, chief executive officer of Exelixis, said, “We will continue to work with Genentech on the evaluation of cobimetinib’s potential in other tumor types, including in melanoma, in which there are two ongoing Phase III pivotal trials. Separately, Exelixis remains focused on and committed to maximizing the potential of the cabozantinib franchise through our commercial activities and ongoing clinical development program evaluating the compound alone, or in combination with immune checkpoint inhibitors, across numerous tumor types.”

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