On January 13, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that the company has entered into a supply agreement with Janssen Research & Development, LLC, a Johnson & Johnson company, to evaluate ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, in combination with subcutaneous (SC) amivantamab, Johnson & Johnson’s fully-human EGFR-MET bispecific antibody, for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (Press release, ORIC Pharmaceuticals, JAN 13, 2025, View Source [SID1234649668]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the agreement, ORIC will conduct and sponsor the trial and Johnson & Johnson will provide SC amivantamab. ORIC maintains development and commercial rights to ORIC-114 and is free to expand the program in combination with other agents.

"ORIC-114 has already demonstrated encouraging systemic and intracranial activity in heavily pre-treated patients with EGFR/HER2 mutated NSCLC," said Jacob M. Chacko, MD, chief executive officer. "Given the prevalence of brain metastases across all lines of EGFR exon 20 NSCLC, we aim to further explore ORIC-114’s emerging profile in the first-line setting both as a monotherapy and in combination with SC amivantamab."

ORIC expects to initiate the combination Phase 1b trial to evaluate the safety and tolerability of ORIC-114 in combination with SC amivantamab for the first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations in the first quarter of 2025. The primary objectives are to determine the provisional recommended Phase 2 dose (RP2D) for the combination, and additional objectives include assessment of efficacy and further characterization of the safety profile of ORIC-114 in combination with SC amivantamab. The company expects to report initial data from the trial in mid-2026.

In 2024, the company announced the completion of the monotherapy dose escalation portion of the Phase 1b trial of ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications. Based upon these data, ORIC selected the two provisional RP2D levels of ORIC-114 at 80 mg and 120 mg QD, which are being further evaluated in three dose expansion cohorts for dose optimization and final RP2D selection in patients with NSCLC with EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, or EGFR atypical mutations as well as an extension cohort for the treatment of patients with first-line, treatment-naïve EGFR exon 20 mutated NSCLC.

About ORIC-114

ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.