Dr Pietrantonio on Future Directions of Evaluating Amivantamab in CRC

“There is also space to investigate amivantamab [in] other tumor types, not limited to GI cancers, but to other tumors with potential sensitivity to EGFR inhibition. There is a lot of space to also investigate biomarkers.”

Filippo Pietrantonio, MD, a medical oncologist and head of the Gastrointestinal Oncology Unit at Fondazione IRCCS Istituto Nazionale dei Tumori, highlighted future directions of evaluating amivantamab-vmjw (Rybrevant) in colorectal cancer (CRC).

The phase 1b/2 OrigAMI-1 trial (NCT05379595), updated findings from which were presented at the 2025 Gastrointestinal Cancers Symposium, evaluated amivantamab monotherapy with or without standard-of-care chemotherapy in patients with advanced or metastatic CRC. At a median follow-up of 8.1 months (range, 0.6-20.3), patients treated with amivantamab monotherapy (n = 23) achieved an objective response rate (ORR) of 22% (95% CI, 8%-44%), a median duration of response (DOR) of 9.8 months (95% CI, 3.7-not evaluable [NE]), a disease control rate (DCR) of 78% (95% CI, 56%-93%), and a median progression-free survival (PFS) of 3.7 months (95% CI, 3.4-5.5). At a median follow-up of 8.2 months (range, 3.2-11.9) in the amivantamab plus FOLFOX or FOLFIRI arm, patients (n = 7) experienced an ORR of 43% (95% CI, 10%-82%), a median DOR of NE (95% CI, 5.8-NE), a DCR of 86% (95% CI, 42%-100%), and a median PFS of 7.4 months (95% CI, 1.8-NE).

Currently, clinical development in the CRC space is expansive, Pietrantonio began. Following the OrigAMI-1 trial, he explained that a pair of phase 3 studies were launched to further evaluate amivantmab in metastatic CRC. These include the OrigAMI-2 trial (NCT06662786) assessing amivantamab vs cetuximab both with or without chemotherapy as first-line therapy and the OrigAMI-3 trial (NCT06750094).

Looking ahead, he noted that there is also room to continue evaluating amivantamab beyond gastrointestinal cancers, especially tumor types that have potential sensitivity to EGFR inhibition. Additionally, there is room to further investigate biomarkers, he added. Of note, patients in the OrigAMI-1 trial harbored a variety of genomic alterations known for resistance to EGFR inhibition, he emphasized. Notably, patients on the study had alterations including TP53, APC, MAP2K1, ATM, ARID1A, PIK3CA, RB1, PTEN, KRAS, FBXW7, EGFR, CDKN2A, and BRAF mutations. Pietrantonio concluded that further research is also needed to identify ways to overcome resistance to first-generation inhibitors in CRC.