A new late-stage clinical trial has received clearance from the U.S. Food and Drug Administration for PT-112, an experimental therapy targeting metastatic castration-resistant prostate cancer (mCRPC). The green light follows a successful End-of-Phase-2 meeting, signaling regulatory confidence in the drug’s development pathway and opening the door to pivotal testing in a patient population with limited remaining options.

PT-112 is the first small-molecule conjugate of pyrophosphate in clinical development for oncology. Its mechanism includes inhibition of ribosomal biogenesis, which triggers immunogenic cell death—a form of tumor cell death that releases damage-associated molecular patterns, or DAMPs, which activate dendritic cells and recruit immune effector cells to the tumor microenvironment. This dual action is particularly relevant for patients with advanced prostate cancer, where treatment resistance is common and durable responses are rare. In addition to its immune-modulating effects, PT-112 displays osteotropism, or a tendency to concentrate in bone tissue, making it especially suited for cancers that metastasize to the skeleton.

The FDA’s decision builds on earlier clinical studies. In the Phase 1 dose-escalation trial, PT-112 was evaluated for safety and tolerability in 66 heavily pre-treated patients with advanced solid tumors, including prostate cancer.
Results showed that 17% of participants achieved progression-free survival of six months or more. Among those with mCRPC, 10 patients exhibited reductions in radiographic lesions and serum tumor markers. Four of these individuals survived for two years or longer—an encouraging outcome in this setting.

The safety profile was also notable. Grade 3 adverse events occurred in 27% of patients, but no grade 4 or 5 events were observed.
The upcoming Phase 3 trial will evaluate PT-112 as a monotherapy in patients who have exhausted other treatment avenues, including at least one next-generation hormonal agent and a taxane-based chemotherapy.

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