- Following the deaths of four patients, Roche said in a statement sent to BioPharma Dive that it has "made a decision to temporarily halt recruitment in the MODUL Phase 2 signal seeking study for metastatic colorectal cancer" following a recommendation from an independent data monitoring committee. The study is assessing the combination of Tecentriq (atezolizumab) and Cotellic (cobimetinib) as maintenance treatment.
- The patient deaths were earlier reported in BioCentury, which said that just one was treatment related (cardiogenic shock); two followed on from disease progression and the other was undisclosed but unrelated to the treatment.
- Review of the safety data found no new safety findings compared with existing data. The decision to pause the study will not affect other trials involving the PD-L1 inhibitor Tecentriq and the MEK inhibitor Cotellic.
Combination therapeutics have long been the mainstay of cancer therapy, and immuno-oncology combo studies have raised hope for many patients, with around 500 combination trials of PD-1/L1 kicking off in 2017.
However, combination studies can throw up unexpected adverse effects, and even though this study has apparently shown no new safety findings based on the review of the safety data for this cohort, the independent data monitoring committee has decided to call a halt.
Roche defended the study design.
"There is a scientific rationale for the combination and we have seen encouraging early efficacy data as well as a consistent safety profile in other settings, however as patient safety is our number one priority we are taking this proactive step to ensure we appropriately evaluate the combination in the maintenance setting," it said in a statement.
Roche remains in discussion with the IDMC, and will collaborate to determine the next steps for the MODUL trial. Other studies looking at the combination are unaffected. These include the IMblaze370 trial in third-line metastatic colorectal cancer. Topline results for this Phase 3 trial are expected in the first half of 2018.
The checkpoint inhibitor market is increasingly heavily contested, with five PD-1/L1 targeting drugs available in the U.S., and around forty following on at various stages in the pipeline. Tecentriq is currently approved for two indications, lagging behind Keytruda (pembrolizumab) and Opdivo (nivolumab).