TAGNOT: A phase 1b/2 tumor-agnostic study of the selective anti-FGFR1 monoclonal antibody OM-RCA-01 in FGFR1-expressing advanced solid tumors.

Abstract

TPS3166 Background: Fibroblast growth factor receptor 1 (FGFR1) plays a key role in the pathogenesis of multiple malignancies; however, no highly selective FGFR1-targeted therapies for solid tumors are currently approved. OM-RCA-01 is a humanized monoclonal antibody that selectively binds extracellular domains II–IIIc of FGFR1 with high affinity (Kd = 1.59 nM) and has demonstrated promising antitumor activity in preclinical models. In the first-in-human, tumor-agnostic (TAGNOT) study, patients with FGFR1-expressing advanced cancers are being treated with OM-RCA-01. Methods: TAGNOT is a phase 1b/2, multicenter, multicohort, prospective study designed according to the FDA-recommended OPTIMUS approach. Key eligibility criteria include FGFR1 expression by immunohistochemistry (IHC 2+ or 3+ in ≥10% of tumor cells) and metastatic disease progressing after ≥2 prior systemic treatment lines. The primary objective of the phase 1b component is to determine the recommended phase 2 dose (RP2D). Two dose levels of OM-RCA-01 (50 mg and 100 mg administered intravenously every 2 weeks) will be compared for safety (CTCAE v5.0), preliminary efficacy (objective response rate [ORR] per RECIST v1.1), pharmacokinetics, neutralizing antibody formation, and circulating tumor DNA dynamics. The primary endpoint of the phase 2 component is ORR in the ITT population. Five tumor-specific cohorts are planned: clear-cell renal cell carcinoma (n = 11), castration-resistant prostate cancer (n = 11), non-small cell lung cancer without EGFR or ALK alterations (n = 11), breast adenocarcinoma with known receptor status (n = 11), and head and neck squamous cell or salivary gland carcinomas (n = 11). Using Simon’s two-stage design, a total of 55 patients will be enrolled. The null hypothesis of a true ORR of 10% will be tested against a one-sided alternative of 25%. The study will be terminated after the first stage if ≤3 responses are observed among 31 patients. Otherwise, 24 additional patients will be enrolled. The null hypothesis will be rejected if ≥10 responses are observed in 55 patients, yielding a one-sided type I error rate of 0.05 and 90% power. Clinical trial information: NCT07292168 .