Phase 2 saruparib tests PARP1 inhibition in HRD-signature-positive solid tumors without prior platinum resistance

This Abramson Cancer Center/Penn Medicine Phase 2 study evaluates saruparib (AZD5305), AstraZeneca’s selective PARP1 inhibitor, in measurable, progressing, locally advanced or metastatic solid tumors with a positive homologous recombination deficiency signature (HRDsig) using an investigational FoundationOne CDx-based trial assay. Cohort A additionally requires a pathogenic germline or somatic variant in BRCA1, BRCA2, PALB2, RAD51B, RAD51C, RAD51D, or BARD1; response in this cohort is the primary efficacy endpoint.

Important tumor-type restrictions distinguish the cohorts: breast, ovarian, prostate, and pancreatic cancers are excluded from Cohort A, and ovarian cancer is excluded from Cohort B. The trial excludes platinum resistance, defined by progression within 6 months of platinum exposure, but allows platinum-naive patients; previous platinum sensitivity is therefore not a universal prerequisite. The study asks whether an HRD signature can identify additional responsive cancers beyond established PARP-inhibitor populations. The assay is investigational in this setting, and its ability to predict benefit across tumor types remains part of the research question.