Pacritinib in Participants With mCRPC Expressing Stat5 (POSTPONE)

To join the phase 2 POSTPONE trial investigating pacritinib for advanced prostate cancer, patients must have metastases that are strongly positive for STAT5 activation—specifically, a recent tumor biopsy must show detectable nuclear STAT5 in more than 5% of cancer cells.​

This trial is built upon robust laboratory and clinical findings showing that the JAK2-STAT5 pathway is a key engine of resistance to androgen receptor signaling inhibitors (ARSI) in metastatic castrate-resistant prostate cancer. ARSI therapies can paradoxically drive activation of the JAK2-STAT5 feed-forward loop, which in turn amplifies JAK2 itself and supports persistent cancer growth even as androgen signaling is blocked. Notably, about a third of these cancers develop STAT5 gene amplification, further fueling this resistance circuit.​

By requiring confirmed STAT5 activation for enrollment, a strategy informed by earlier evidence that only this molecular subgroup responded in previous trials, the POSTPONE study pursues a highly personalized approach. The aim is to selectively disrupt this axis in those most likely to benefit, using pacritinib, a potent JAK2/IRAK1 inhibitor with a favorable safety profile from hematologic malignancy trials. Preliminary data have shown that JAK2-STAT5 blockade induces apoptosis in prostate cancer models surviving ARSI therapy, supporting the biologic basis for this focused trial.​

Clinical trial.