Roche is the latest company to have clinical trials with a checkpoint inhibitor put on hold by the U.S. Food and Drug Administration (FDA). Trials with Tecentriq® (atezolizumab) were put on hold on September 18th, and follows the decision by the FDA in July this year to call a stop to clinical trials with Merck’s Keytruda® (pembrolizumab), as well as a partial halt on trials with Bristol-Myers Squibb’s Opdivo® (nivolumab), AstraZeneca’s Imfinzi (durvalumab) and MerckKGaA and Pfizer's Bavencio (avelumab). All of these were also being tested in combination therapies for MM.
This domino effect follows a higher than average number of deaths in the pembrolizumab trials, which raised concerns that there may be an inherent safety issue with this class of drug when used in certain combinations – see previous MM Hub article. This has bought the FDA more time to gather details, as patient safety remains their priority.
In this latest decision, the trials called to a halt were early phase Ib and phase Ib/II trials, assessing the efficacy of atezolizumab in combination with either lenalidomide (Revlimid®, Celgene) or pomalidomide (Pomalyst®, Celgene) to treat Relapsed/Refractory Multiple Myeloma (RRMM).
Atezolizumab is a monoclonal antibody against PD-L1 (programmed death-ligand 1), which already has FDA approval to treat a number of other cancers, including lung and bladder cancer. Interestingly, no safety concerns have been raised prior to this, suggesting that only in this setting may it pose a problem. Whilst the role of the PD-1/PD-L1 axis is well understood, the interplay with other signals specifically in MM has yet to be fully described, as well as the synergistic effect of combining the different regimens, in particular with other immunomodulatory drugs (IMiDs). Answering this key question is likely to be on the agenda in many research labs going forward.