Adham Jurdi, Sr Medical Director of GI Oncology and Innovations at Natera, shared on LinkedIn:
“UNICORN is out in Nature Portfolio, Nature Medicine today. Patients with resectable colon cancer got one dose of Botensilimab, with or without two doses of Balstilimab, then went to surgery around day 35.
Our team at Natera ran the ultrasensitive Signatera Genome on serial plasma from 51 patients. A few results stand out:
Every pMMR major responder cleared ctDNA. In pMMR disease, every patient started ctDNA-positive. Six cleared by surgery, all on the combination. Five of them were the five major pathologic responders. The sixth had 30% residual tumor and has not recurred, which raises the question of whether partial responders who clear ctDNA do as well as major responders (in the context of surgical resection).
Clearance closely mirrored pathologic response. Almost every non-responder, pMMR or dMMR, was still positive at surgery. Across the trial, clearance and major pathologic response agreed almost completely (φ = 0.92), so ctDNA clearance may serve as a surrogate for pathologic response. A non-invasive readout like that is what non-operative strategies will need. Nobody who cleared has recurred so far.
Quantitative levels added information. One dMMR patient had a pCR but never fully cleared. Their level dropped from 170 to 1.37 MTM/mL, so a simple positive/negative read before surgery would have missed that pCR.
Congratulations to the patients, Filippo Pietrantonio Filippo Ghelardi and the rest of the UNICORN investigators, Steven O’Day and the Agenus team, and my Natera colleagues Stephanie Ni, Darryl Nousome Erik Spickard, Tony Tin and Robert Lentz.”
Title: Neoadjuvant botensilimab with or without balstilimab in pMMR and dMMR colon cancer: the phase 2 UNICORN trial
Authors: Filippo Ghelardi, Margherita Ambrosini, Alessandra Raimondi, Andrei Tyshevich, Federica Palermo, Francesca Bergamo, Vincenzo Nasca, Paolo Manca, Ilaria Mulas, Lisa Derosa, Gina Brown, Claudia Chiodoni, Massimo Di Maio, Samantha Di Donato, Anna Chiaramonte, Lorenzo Castagnoli, Stephanie Ni, Darryl Nousome, Erik Spickard, Antony Tin, Robert Lentz, Adham Jurdi, Giovanna Sabella, Daniele Spada, Stefano Tamberi, Alessandro Passardi, Federica Morano, Emiliano Tamburini, Chiara Rossi, Luca Azzolin, Francesco Cambuli, Antonia Martinetti, Elisa Sottotetti, Andrew Allan Almonte, Valerio Iebba, Chiara Ratti, Riccardo Cerantola, Özlem Kutlu, Eleonora Cristarella, Serenella M. Pupa, Cecilia Villa, Eleonora Perissinotto, Margherita Galassi, Andrea Barina, Fabrizio Vittadello, Marcello Guaglio, Gianluca Baiocchi, Andrea Sartore-Bianchi, Riccardo Rosati, Chiara Cremolini, Isacco Montroni, Sara Lonardi, Andrea Sottoriva and Filippo Pietrantonio.
Read the full article.
Learn more: UNICORN Challenges Immunotherapy Resistance in MSS Colon Cancer
