PNT6555 is an early-stage radioligand that targets Fibroblast Activation Protein-α (FAP-α), which is highly expressed on a wide range of solid tumors. PNT6555 was developed in collaboration with Dr. William Bachovchin at Tufts, a leader in designing inhibitors of DASH family proteases, including FAP.
FAP-α is a compelling pan-cancer target for imaging and therapy because it is found in greater than 90% of epithelial tumors.
PNT6555 targets FAP-α with best-in-class tumor retention and normal tissue clearance, exhibiting ideal radiopharmaceutical characteristics: delivery of large doses of radiation directly to a wide variety of tumors while being flushed from healthy tissues.
The Phase 1 clinical trial ("FRONTIER") commenced in the summer of 2022 in Canada and uses a gallium-68 (68Ga)-based PNT6555 molecular imaging agent to select patients to receive a no-carrier-added (n.c.a.) lutetium-177 (177Lu)-based PNT6555 therapeutic agent. The Phase 1 clinical protocol evaluates PNT6555 in ~30 patients in five FAP-avid cancer indications: colorectal, pancreatic, esophageal, melanoma, and soft tissue sarcoma.
Dosing will start at 4 GBq with each subsequent dose level increasing by 4 GBq and 2 GBq dose de-escalations. Each 177Lu PNT6555 dose will be followed by a 6-week interval. 68Ga-PNT6555 PET/CT imaging will be conducted approximately 90 minutes post injection, and dosimetry will be completed at the time of first 177Lu-PNT6555 dose and each subsequent cycle. The primary objective of the study is to determine the maximum tolerated dose (MTD), and the Recommended Phase II Dose (RP2D).