763P - Re-VOLVE: Phase II trial in women with ovarian cancer progressing post-PARP-inhibitor with treatment adapted to real-time assessment of evolving genomic resistance

Background

Despite clinical success of PARP inhibitors (PARPi) in high-grade serous ovarian cancer (HGSOC), a significant proportion of patients (pts) develop recurrence. Many PARPi resistance mechanisms have been described. We report the results of first-stage of phase II in women with HGSOC post-PARPi with treatment adapted to real-time assessment of evolving genomic resistance (NCT05065021).

Methods

This pilot study enrolled pts to initial phase: 2-3 cycles of niraparib (200-300mg/OD)/ bevacizumab (7.5mg/kg/q3w), followed by personalized phase: (A) niraparib/bevacizumab/dostarlimab (500mg/q3w), (B) paclitaxel (80mg/m² weekly)/bevacizumab/dostarlimab, or (C) continue niraparib/bevacizumab, based on initial response and real-time assessment from baseline tumor biopsy (genome/RNA sequencing) and ctDNA (12-gene-panel). Purpose of the first stage was to determine feasibility of using real-time molecular profiling results to guide personalized therapy. Feasibility was achieved if >80% had ctDNA and/or baseline tumor genomic guided treatment.

Results

Of 31 pts enrolled, 20 completed first-stage. Fourteen pts had baseline ctDNA and tissue biopsy to guide therapy and 6 ctDNA alone (100%). From pts with both samples, TP53 mutations were detected in 71.4% of ctDNA and 100% of biopsies. Mechanisms of resistance were detected in 3 pts: 1 CHEK2 mutation and 2 CCNE1-amplification. Grade 3 AE related to therapy in 30%; no grade 4 AE. Of 15 pts whose best response were evaluated (five too early to assess; personalized-phase), 6 achieved partial response (40%; 3 Pr and 3 Ps) and eight (53.3%) stable disease (5 Pr and 3 Ps). Table: 763P

Conclusions

Re-VOLVE study has met stage 1 requirements and currently expanding to stage 2 with 20 additional pts. This phase II study shows feasibility to guide personalized therapy in real-time in recurrent OC post-PARPi. ctDNA may require broader, more sensitive methods to best guide decision-making.

Clinical trial identification

NCT05065021.

Editorial acknowledgement

Legal entity responsible for the study

UHN.

Funding

GSK and Apotex.

Disclosure

V. Bowering: Non-Financial Interests, Advisory Role, Nurses Advisory board - Lynparza: AstraZeneca; Non-Financial Interests, Advisory Role, Nurses Advisory Role- Niraparib: GSK. S. Lheureux: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Seagen, Eisai, Repare, Schrodinger; Financial Interests, Institutional, Funding: Repare, Roche, AstraZeneca, GSK; Financial Interests, Institutional, Local PI: Merck. All other authors have declared no conflicts of interest.