Abstract
LODESTAR: A single-arm phase II study of rucaparib in solid tumors with pathogenic germline or somatic variants in homologous recombination repair genes
Journal of clinical oncology, Vol.43(16_suppl), pp.3151-3151
06/2025
DOI: 10.1200/JCO.2025.43.16_suppl.3151
Abstract
3151
Background: To explore PARP inhibitor (PARPi) utility across solid tumors and identify biomarkers that predict sensitivity. Methods: This single-arm phase II study assessed rucaparib monotherapy in patients with solid tumors and pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D (Cohort A) or BARD1, BRIP1, FANCA, NBN, RAD51B (Cohort B). The primary endpoint was ORR in Cohort A. Secondary endpoints included DCR, PFS, OS and safety. A scar-based HRD signature (HRDsig) and platinum sensitivity status were explored post-hoc. Results: Fifty-one patients in Cohort A and 12 in Cohort B were evaluable for efficacy. ORR of cohort A was 18% (95% CI 10-30%). A significantly higher ORR was observed with HRDsig+ tumors compared to HRDsig- tumors (32%, 95% CI 15-54, vs. 0%, 95% CI 0-14%, p < 0.01). In the entire study population: DCR of 65% (95% CI 53-76%), mPFS of 5.5 mo (95% CI 3.68-7.82), and mOS of 12.1 mo (95% CI 10.6 – inf). PFS and OS were significantly longer for platinum sensitive tumors (mPFS: 7.8 mo vs. 3.5 mo, p = 0.02; mOS: NR vs 5.45mo, p = 0.01). Tumor histology was not independently predictive of outcome. Tumors with PVs in Cohort A genes were more likely to be HRDsig+ than tumors with PVs in Cohort B genes. Analysis of a large commercial database showed that in non-canonical tumors with BRCA PVs, 30.2% were HRDsig+. Conclusions: Rucaparib has activity in HRDsig+ solid tumors with PVs in HRR genes, regardless of histology. Platinum sensitivity correlated with improved outcomes. Clinical trial information: NCT04171700 .
Details
- Title: Subtitle
- LODESTAR: A single-arm phase II study of rucaparib in solid tumors with pathogenic germline or somatic variants in homologous recombination repair genes
- Creators
- Sriram Anbil - University of Pennsylvania Health SystemNicholas Seewald - University of PennsylvaniaE. Gabriela Chiorean - Fred Hutch Cancer CenterMaen A. Hussein - Florida Cancer Specialists & Research InstitutePashtoon Murtaza Kasi - NewYork–Presbyterian HospitalDouglas Earl Laux - University of IowaGary K. Schwartz - Case Comprehensive Cancer CenterGeoffrey Ira Shapiro - Dana-Farber Cancer InstituteKevin K. Lin - Clovis OncologyMarcia CraibLara Maloney - Clovis OncologyKaren Retta McLachlan - Clovis OncologyHanna Tukachinsky - Foundation MedicineAlexa Betzig Schrock - Foundation MedicineShuoguo WangEthan Sokol - Foundation MedicineBrennan Decker - Foundation MedicineKatherine L. Nathanson - University of PennsylvaniaSusan M. Domchek - Penn Center for AIDS ResearchKim Anna Reiss - University of Pennsylvania
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.43(16_suppl), pp.3151-3151
- DOI
- 10.1200/JCO.2025.43.16_suppl.3151
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984843246602771
Metrics
1 Record Views