A string of deaths in a cohort of colon cancer patients taking a combination of Roche’s PD-L1 checkpoint Tecentriq with Exelixis’ MEK inhibitor Cotellic forced the independent monitoring board to halt enrollment of new patients in their Phase II MODUL study. And Roche says one of those deaths was a treatment-related case of cardiotoxicity.
The study was designed to bring in about 1,400 patients with an eye to divvying them up into various combinations with Tecentriq for metastatic colon cancer. According to a statement from Genentech, investigators opted to take a proactive safety step after seeing an imbalance in patient deaths in this cohort getting the combo as a maintenance therapy for frontline cases of colon cancer, pausing enrollment as treatment continues for the patients already in the study.
From their statement:
The IDMC recommendation followed an observed imbalance in the number of deaths in the experimental arm versus the control arm. At the time of the IDMC review, three deaths occurred on the experimental arm. One death due to cardiogenic shock was treatment related, while the other two deaths were due to disease progression. We recently learned of another death in the Cohort 4 experimental arm, which was documented as not related to study treatment. We are proactively providing the latest information on all the cases to the IDMC.
That interruption, though, won’t slow down IMblaze370, a Phase III study testing the combination for mCRC. Data from that study are due out soon, representing one of the top catalysts for Roche’s big checkpoint campaign in 2018 as it tries to catch up with the leaders at Merck and Bristol-Myers Squibb. The big impact from the readout, though, will lie with Exelixis.
News of the suspension in the study started to spread earlier this week on Twitter, after investigators updated the posting for this trial on clinicaltrials.gov. Then Roche acknowledged the issue with some analysts.
The haphazard communications underscore the fact that there is no standard approach for highlighting safety issues for either experimental or commercial drugs, as Roche demonstrated recently when it sent statements on a series of 5 deaths that occurred among patients taking their big hemophilia drug Hemlibra.
Companies take a variety of approaches to reporting the worst safety cases involving FDA holds, with two biotechs — Solid and Unum — recently choosing to hold back any news on regulatory actions until they had to alert potential investors in their IPOs. It’s particularly easy in the US, as the FDA typically keeps these trial-related events and any involvement they may have as a regulator under wraps.
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