Phase II Trial of TAS-102 in Colorectal Cancer Patients With Circulating Tumor DNA-Defined Minimal Residual Disease After Adjuvant Therapy: INTERCEPT-TT.

Purpose: To determine whether treatment with TAS-102 can induce circulating tumor DNA (ctDNA) clearance at 6 months and delay/prevent disease recurrence in colorectal cancer (CRC) patients with ctDNA-defined minimal residual disease (MRD) after completion of adjuvant therapy.

Patients and methods: This was a single-arm, single-institution, phase II study. Fifteen patients with stage II to IV CRC and ctDNA-defined MRD after curative-intent therapy and adjuvant chemotherapy were enrolled prospectively. Participants received 6 months of therapy with TAS-102 35 mg/m² twice a day on days 1-5 and 8-12 of each 28-day cycle. Disease recurrence was monitored every 3 months with ctDNA and cross-sectional imaging. For comparison, 30 patients matched for key variables who received standard of care were retrospectively identified for a synthetic control (SC) cohort. The primary end point was 6-month ctDNA clearance. Secondary end points included 3-month ctDNA clearance, disease-free survival (DFS), and safety.

Results: Among 15 patients enrolled, median age was 60.2 years (range, 37-73) and 80% were stage IV with an average of 2.1 lines of previous therapy (range, 1-3). At 3 and 6 months, respectively, seven (47%) and five (36%) patients had ctDNA clearance. In the SC, two patients (6.7%) had spontaneous ctDNA clearance at 3 months (P = .0034) sustained at 6 months (P = .025). Among patients receiving TAS-102, nine patients had radiographic recurrence with a median DFS of 9.4 months compared with 28 patients in the SC with radiographic recurrence and a median DFS of 5.75 months (P = .03).

Conclusion: Additional treatment with TAS-102 after adjuvant chemotherapy in CRC patients with ctDNA-defined MRD can induce ctDNA clearance but this may be transient without long-term cures.