Dr Pietrantonio on Amivantamab With/Without Chemotherapy in Right-Sided RAS/BRAF Wild-Type mCRC

“Hopefully we will have space for EGFR inhibition even in patients with right-sided tumors. We know that there is a subgroup of patients with potential benefit from this strategy, and we may potentially extend the number of patients with potential benefit from the use of…amivantamab.”

Filippo Pietrantonio, MD, medical oncologist, head, Gastrointestinal Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, discusses longer follow-up data from the phase 1b/2 OrigAMI-1 trial (NCT05379595) assessing amivantamab as monotherapy and in combination with chemotherapy in metastatic colorectal cancer (mCRC).

Updated findings presented during the 2025 Genitourinary Cancers Symposium showed durable antitumor activity with amivantamab as both a single agent and in combination with chemotherapy among heavily pretreated patients with right-sided RAS/BRAF wild-type mCRC, Pietrantonio reports. The agent’s safety profile was also consistent with prior reports, he adds.

In the third-line setting and beyond, amivantamab monotherapy (n = 23) achieved an objective response rate (ORR) of 22% (95% CI, 8%-44%) and a median progression-free survival (PFS) of 3.7 months (95% CI, 3.4-5.5). When amivantamab was combined with chemotherapy (n = 7), the ORR increased to 43% (95% CI, 10%-82%) with a median PFS of 7.4 months (95% CI, 1.8-not evaluable) despite the limited number of patients receiving the combination in this study, Pietrantonio notes. These findings highlight the potential efficacy of amivantamab, even in patients with right-sided mCRC, a population traditionally less responsive to EGFR inhibition, he says.

Currently, 3 clinical trials—the phase 3 OrigAMI-2 trial (NCT06662786), the phase 3 OrigAMI-3 trial (ISRCTN39913423), and another phase 2 study—are ongoing to further evaluate the efficacy of amivantamab in earlier mCRC treatment settings, Pietrantonio continues. OrigAMI-2 is investigating amivantamab plus doublet chemotherapy compared with cetuximab (Erbitux) plus chemotherapy in patients with left-sided RAS/BRAFwild-type mCRC in the first-line setting. OrigAMI-3 is evaluating amivantamab plus FOLFIRI (folinic acid, fluorouracil, and irinotecan) vs FOLFIRI vs cetuximab or bevacizumab (Avastin) in the second-line setting, irrespective of primary tumor location, among patients with RAS/BRAF wild-type tumors.

The potential benefit of amivantamab in patients with right-sided mCRC is particularly significant given the limited efficacy of current EGFR inhibitors in this population, Pietrantonio says. These trials may expand the role of EGFR inhibition to a broader patient cohort, offering a promising therapeutic strategy for those with limited treatment options, he explains. The ongoing studies will clarify the efficacy and safety of amivantamab across different lines of therapy and tumor locations, potentially redefining the standard of care for RAS/BRAF wild-type mCRC, Pietrantonio concludes.