TEST:

Signatera™

Treatment consists of pembrolizumab 200 mg and cisplatin 80 mg/m2 IV day 1, and continuous 5-fluorouracil 800 mg/m2/day on days 1-5 every 3 weeks for four cycles, with SCRT of 25 Gy in five fractions on days 8-12 of cycle 1. Exploratory endpoints include analysis of molecular residual disease using a personalized, tumor-informed circulating tumor DNA assay (SignateraTM, Natera, Inc., Austin, TX) and translational studies. Planned enrollment is 35 patients, assuming a threshold 2-year OS rate of 30% and an expected rate of 50%, with one-sided α of 0.10 and 80% power.

A personalized surgical approach to neoadjuvant ICI was feasible, with comparable recurrence rates between the patients who underwent INE and those who underwent TLND. For the patients without MPR, subsequent adjuvant therapy improved recurrence-free survival (p = 0.046). The ctDNA results correlated with the clinical outcomes, suggesting that ctDNA may complement pathologic response in guiding management.

"Natera, Inc...today announced that the U.S. Food and Drug Administration (FDA) has approved Signatera CDx as a companion diagnostic (CDx) for use with adjuvant atezolizumab (Tecentriq®) immunotherapy in MIBC."

P=N/A, N=30, Suspended, Rutgers, The State University of New Jersey | Trial completion date: Nov 2024 --> Sep 2027 | Recruiting --> Suspended | Trial primary completion date: Nov 2024 --> Jun 2027

P=N/A, N=1000, Not yet recruiting, Natera, Inc.

MRD was highly specific but less sensitive. Prospective studies are needed to define optimal testing intervals and validate MRD-guided strategies.

P2, N=20, Not yet recruiting, National Cancer Institute (NCI)

P4, N=90, Recruiting, NYU Langone Health | Not yet recruiting --> Recruiting

P2/3 | "Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA– (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines v serial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos...Dasari and Lieu contributed equally to the development of this trial. NCT05174169."

P2, N=15, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P=N/A, N=50, Active, not recruiting, Nagoya City University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P1, N=22, Recruiting, University of California, Irvine | Trial completion date: Dec 2026 --> Jan 2028 | Trial primary completion date: Dec 2025 --> Jan 2027