HITMAN-PC Phase 1 Results: Hydroxychloroquine + SUBA-Itraconazole Stabilizes Biochemical Prostate Cancer Relapse

The HITMAN-PC trial represents a targeted metabolic approach to managing biochemical relapse in prostate cancer, combining hydroxychloroquine (HCQ) and SUBA-itraconazole (SI) to disrupt lysosomal function and cholesterol trafficking in hormone-sensitive disease. In this phase 1 dose-escalation study, 11 men (median age 73, baseline PSA 4.4 ng/mL, PSA doubling time 5.3 months) received fixed SI at 150 mg twice daily with escalating HCQ up to 600 mg twice daily. No dose-limiting toxicities occurred below HCQ 600 mg BD (where two grade 3 events, diarrhea and ALT elevation, emerged).

While no patients achieved a PSA decline of ≥50%, the regimen stabilized disease effectively, yielding a median PSA progression-free survival (PSA-PFS) of 5.5 monthsand time-to-ADT of 14.3 months exceed typical untreated doubling times (baseline 5.3 months), implying disease control in this high-risk cohort. Metastasis-free survival at 15.9 months supports potential to postpone systemic therapy in hormone-sensitive relapse.
These outcomes suggest meaningful control in a high-risk group awaiting aggressive intervention, outperforming natural history in some observational benchmarks for biochemical recurrence post-prostatectomy or radiation. Comprehensive lipidomic profiling revealed 240 treatment-associated changes, notably in sphingomyelin and triacylglycerol species that correlated with PSA-PFS, providing pharmacodynamic evidence of target engagement and potential biomarkers for patient selection in future studies.

NOTE: Without a control arm or statistical comparisons, these metrics suggest target engagement (via lipid changes) but no clear superiority over watchful waiting, underscoring the need for phase 2 randomization to prove delayed ADT benefit (14.3 months here).

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