Genomically matched therapy in advanced solid tumors: the randomized phase 2 ROME trial

Despite recent advancements demonstrating the potential of tumor-agnostic biomarkers to guide effective therapies, randomized evidence supporting the clinical superiority of precision oncology approaches compared to standard therapies remains limited. The ROME trial was a multicenter, randomized, open-label phase 2 study comparing tailored treatment (TT) to standard of care (SoC) in patients with advanced solid tumors progressing after one or two lines of therapy. Comprehensive genomic profiling on tissue and blood was performed to identify actionable alterations. Overall response rate (ORR) was the primary endpoint, and progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), time to next treatment (TTNT) and safety were the secondary endpoints. Between November 2020 and August 2023, 1,794 patients were screened, 897 were evaluated by the molecular tumor board (MTB) and 400 were randomized to TT or SoC. TT achieved a significantly higher ORR (17.5% versus 10%; P = 0.0294) and improved median PFS (3.5 months versus 2.8 months; hazard ratio = 0.66 (0.53–0.82), P = 0.0002). TT also showed superior 12-month PFS rates (22.0% versus 8.3%). Median OS was similar, with a 52% crossover rate. Grade 3/4 adverse events were also similar (40% TT versus 52% SoC). These results highlight the potential of TT to improve outcomes for patients with diverse actionable genomic alterations. These results also provide relevant evidence supporting a tumor-agnostic precision oncology strategy and highlight the potential of TTs, guided by genomic profiling and MTB recommendations, to significantly improve outcomes for patients with diverse actionable genomic alterations. ClinicalTrials.gov identifier: NCT04591431.