A Battle of Biblical Proportions: AdAPT-001 vs. Metastatic Cancer

Aug 16, 2023

With the tech gladiator fight between Elon Musk and Mark Zuckerberg now reportedly off, let’s recap Round 1 of the much more significant and important battle between AdAPT-001 and refractory cancer that took place earlier this year.

The Goliath in this case was/is metastatic cancer at a weight of several hundred grams and “height” (longest diameter) between 1-10 cm. The David-like challenger was/is AdAPT-001 at about one-billionth of 1 gram and “height” (diameter) of about 90 nanometers. For reference, a nanometer is one ten-millionth of a centimeter or 10-7 centimeters. All in all, this makes tumors a billion times heavier and 10 million times “taller” than AdAPT-001 for a true David vs. Goliath life-and-death match-up.

AdAPT-001, an adenoviral delivery vector, relies on fast replication kinetics and a “slingshot” in the form of a transforming growth factor-beta or TGF-β trap that it carries to even the odds against its much larger and heavier adversary. This TGF-β trap “slingshot” neutralizes one of the tumor’s greatest weapons, the overexpressed immunosuppressive TGF-β cytokine that puts the host immune system to sleep.

The main takeaways from this Phase 1 trial were as follows:

  • AdAPT-001 was well tolerated with transient local inflammation, fever, and fatigue as the main side effects. No dose limiting toxicities or related serious adverse events (SAEs) occurred, and no maximal tolerated dose was reached. The top dose was 1×1012 viral particles (VPs) injected once every 2 weeks.
  • Out of 28 patients, most with non-immunogenic tumors, the overall responses to treatment included 3 confirmed partial responses, 5 patients with durable stable disease > 6 months, and 13 patients with progressive disease.
  • Systemic or abscopal activity in non-injected lesions was definitively observed, which suggests body wide immune activation.

Currently ongoing is Round 2 of this battle, a Phase 2 trial with AdAPT-001 and checkpoint inhibitors in checkpoint inhibitor-refractory tumors. Next up after that is a Phase 2 trial in metastatic colorectal cancer with systemically administered AdAPT-001.

As legendary ring announcer, Michael Buffer, might intone, were he to ever emcee this impending match-up, “on behalf of millions of cancer patients around the world, let’s get ready to rumble!