ORIC Pharmaceuticals Shows Complete Systemic And CNS Responses In NSCLC With Enozertinib A Brain-Penetrant EGFR Exon 20 Inhibitor

ORIC Pharmaceuticals, Inc., a clinical-stage oncology company developing therapies to overcome cancer resistance mechanisms, announced the publication of a peer-reviewed study in Cancer Research, the journal of the American Association for Cancer Research. The paper outlines the discovery and development of enozertinib (previously known as ORIC-114), a next-generation, highly brain-penetrant EGFR exon 20 inhibitor that is orally available and exhibits exceptional kinome selectivity.

EGFR mutations are key oncogenic drivers in non-small cell lung cancer (NSCLC), and nearly half of patients are likely to develop brain metastases during disease progression. Those with non-classical EGFR mutations, including exon 20 insertions, typically experience poorer clinical outcomes compared to patients with classical EGFR mutations. Current therapies have limited intracranial efficacy, creating an urgent need for selective, brain-penetrant inhibitors that can effectively target resistant tumor types and improve patient prognosis.

“These studies affirm our belief that enozertinib is uniquely positioned to address the unmet needs in patients with NSCLC driven by EGFR exon 20 and atypical mutations,” said Melissa Junttila, PhD., vice president, head of biology at ORIC, and first author of the publication. “We look forward to sharing additional clinical data for enozertinib later this year and in mid-2026 and further elucidating its best-in-class potential.”

The Cancer Research paper presents preclinical data showcasing enozertinib’s potent and selective activity across multiple atypical EGFR mutations, alongside its robust anti-tumor effects in brain tumor models. It also highlights a remarkable clinical case in which a patient with NSCLC harboring an EGFR exon 20 insertion mutation achieved a complete systemic and CNS response, with sustained tumor regression following enozertinib treatment. To date, enozertinib is the only EGFR exon 20 inhibitor reported to produce both systemic and brain complete responses in a patient with untreated, active brain metastases.