New Year’s Revolution

Jan 11, 2024

Vive la révolution! The immunotherapy revolution.

Having begun in 2011 with the approval of the first immune checkpoint inhibitor (ICI), ipilimumab (Yervoy), we predict that 2024 will continue the revolution with the advancement of therapies that reverse resistance to ICIs, so prevalent in most patients.

One of these potentially resistance-reversing therapies is the oncolytic adenovirus, AdAPT-001. An ongoing Phase 2 clinical trial has demonstrated evidence of tumor elimination when AdAPT-001, which expresses a transforming growth factor-beta (TGF-β) trap that binds to and neutralizes the pro-cancer cytokine, TGF-β, is combined with a PD-1/L1 checkpoint inhibitor. This is the case even in some patients who previously received—and failed—a PD-1/L1 checkpoint inhibitor.

Which is huge. Or potentially huge because around 10-15% of patients— possibly closer to 20% of patients—must stop ICIs early due to the development of the severe sometimes fatal autoimmune-related toxicities that these ICIs cause. To date most other immunotherapies that have been combined with ICIs whether they improve response rates or not worsen their side effect profiles, which is, of course, extremely problematic and a real non-starter.

So far at least this has not been the case with AdAPT-001. One of the main takeaways from the Phase 2 trial besides the even-better-than-expected response rates is the lack of any dose limiting toxicities when AdAPT-001 and an ICI are combined.

Long may these minimally toxic, AdAPT-001-mediated antitumor responses continue.

Vive la virolution!