KEY TAKEAWAYS
- The phase 2 trial aimed to investigate the feasibility and efficacy of therapeutic interventions in CRC patients who test positive for MRD during surveillance.
- The primary endpoint was to determine 6-m ctDNA clearance.
- Researchers noticed promising short-term efficacy of TAS-102 in inducing ctDNA clearance in CRC patients with MRD; further investigation is ongoing.
Circulating tumor DNA (ctDNA) holds promise as a highly specific marker for detecting minimal residual disease (MRD) in colorectal cancer (CRC) patients. However, therapeutic strategies targeting MRD are critical to improving cure rates. While ongoing trials are exploring MRD as a biomarker for post-operative adjuvant therapy intensity, little is known about the feasibility and efficacy of treatment in MRD-positive patients during surveillance following all curative intent treatments, including adjuvant chemotherapy.
Andrew Jared Pellatt and the team aimed to assess the feasibility and efficacy of therapeutic interventions in CRC patients who tested positive for MRD during surveillance.
Researchers performed an inclusive analysis in this proof-of-concept phase II study involving patients diagnosed with stages II-IV CRC who were identified as MRD+ during surveillance (ctDNA+ but no radiographic evidence of disease on imaging in the last 30 days) and received a 6-month course of TAS-102. The MD Anderson INTERCEPT program facilitated the identification of eligible patients, integrating MRD testing using a tissue-informed assay (Signatera) into the standard of care for CRC patients.
The primary endpoint of the study was the clearance of ctDNA at 6 months, with secondary objectives including 3-month ctDNA clearance and assessment of disease-free survival (DFS). The study design assumed a null hypothesis (H0 = 5%) spontaneous ctDNA clearance, with an alternative hypothesis HA = 30% ctDNA clearance with TAS 102 & 1-sided α = 0.05, aiming for a statistical power of 15 patients β of 85%.
About 15 patients with MRD were enrolled between July 22, 2022, and September 7, 2023. Baseline characteristics revealed a median age of 62 years (range: 37-73), with the majority being Caucasian (77%) and male (77%). Most patients had resected Stage IV disease (92%) and a median ctDNA level of 1.55 MTM/ml (range 0.04-28.72). At the data cutoff, 11 patients had 3-month ctDNA levels assessed, with 10 showing a decrease in their ctDNA levels (91%), including 5 patients with undetectable levels (45%).
By 6 months, 60% of patients had ctDNA levels at or below their prior levels, and three patients maintained undetectable ctDNA levels at this time point. However, two of these patients experienced radiographic progression following completion of therapy. The median DFS for the full cohort was 9.4 months.
The trial is sponsored by M.D. Anderson Cancer Center
Source: https://meetings.asco.org/abstracts-presentations/229071
Clinical Trial: https://clinicaltrials.gov/study/NCT05343013
Pellatt A J, Bent A H, Parseghian C M, et al. (2024). “A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy: Results from the MD Anderson INTERCEPT Program.” Presented at ASCO GI 2024 (Abstract 136).
