METEORITE: A phase II study of Y-90, capecitabine, and atezolizumab in oligometastatic CRC (BrUOG430).

Abstract

TPS276 Background: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Patients with microsatellite-stable (MSS), chemotherapy-refractory metastatic CRC have limited treatment options, with third-line treatment offering modest survival benefits. Yttrium-90 (Y-90) radioembolization is an established locoregional therapy that provides intrahepatic disease control, while also exerting immunomodulatory effects that may enhance responsiveness to checkpoint inhibition. Atezolizumab, an anti–PD-L1 antibody, has demonstrated tolerability in CRC in combination with chemotherapy but limited single-agent activity in MSS disease. Capecitabine is a known radiosensitizer commonly used in conjunction with radiation therapy. We hypothesize that Y-90, in combination with capecitabine and atezolizumab, will synergistically improve intrahepatic disease control in patients with chemotherapy-refractory, unresectable, liver-isolated or liver-dominant metastatic CRC. Methods: METEORITE (BrUOG-430) is a prospective, single-arm, phase II pilot trial evaluating Y-90 microspheres with concurrent capecitabine and atezolizumab. Eligible patients must have histologically confirmed CRC with surgically unresectable, liver-isolated or liver-dominant, RECIST-measurable liver metastases, with <50% tumor involvement of the liver, and progression on ≥2 lines of systemic therapy. Patients with MSI-H, dMMR, or high TMB are excluded. All participants will receive atezolizumab 1200 mg IV every 3 weeks for 5 cycles, beginning 14 (±3) days prior to Y-90 treatment. Y-90 is delivered on day 0 (and day 42 if bilobar disease is present), with capecitabine 825 mg/m² PO BID for 14 days following each Y-90 procedure. The primary endpoint is intrahepatic disease control rate (iDCR) at 12 weeks. Secondary endpoints include safety, extrahepatic disease control, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Correlative studies will be performed on serial tumor biopsies, incorporating spatial proteogenomic profiling to assess immunologic and molecular correlates of response, as well as on peripheral blood with circulating tumor DNA (ctDNA). A Simon’s minimax two-stage design is employed: if ≥1/9 patients in stage 1 achieve iDCR, accrual expands to 18 patients. iDCR in ≥7/18 will be considered a signal of efficacy. Accrual is ongoing at Brown University Health Cancer Institute. Enrollment of 18 patients is anticipated to be completed within 24 months, with a total study duration of ~36 months. Clinical trial information: NCT06555133 .