NSABP FC-12: A Single-Arm, Phase II Study to Evaluate Treatment with Gevokizumab in Patients with Stage II/III Colon Cancer Who Remain Ctdna+ after Curative Surgery and Adjuvant Chemotherapy.

TPS3642 Background: Detection of circulating tumor DNA (ctDNA) in patients (pts) following surgery is indicative of presence of minimal/molecular residual disease (MRD) and confers a near-certain risk of disease recurrence. Therapeutic strategies to treat MRD following standard curative therapies are needed because the risk of recurrence is high and therapeutic intervention may provide clinical benefit to patients. Gevokizumab is a recombinant humanized monoclonal antibody targeting interleukin-1β (IL-1β), which is involved in all phases of the malignant process (tumorigenesis, invasion, metastasis, angiogenesis, progression, and the modulation of anti-tumor immunity). Gevokizumab has been validated in pre-clinical colon cancer (CC) models and safety established in the advanced-stage clinical setting. In this trial in progress, we aim to test the efficacy of gevokizumab in pts with early-stage CC with MRD (ctDNA-positivity) following definitive treatment. Methods: NSABP FC-12 is a single-arm, multi-centered phase II study that will include pts with stage II/III CC who test MRD+ within 6 wks following completion of curative surgery and ≥3 mos of adjuvant chemotherapy. MRD will be assessed using a personalized and tumor-informed ctDNA assay (Signatera bespoke assay). Gevokizumab will be given at a flat dose of 120 mg IV every 28 days for 13 cycles. The primary endpoint is relapse-free survival (RFS) following initiation of study therapy through one year of follow-up. Secondary endpoints are rate of ctDNA clearance at 8 wks from start of study therapy, as well as safety, toxicity, pharmacokinetics, and immunogenicity of gevokizumab. Exploratory and correlative endpoints will include outcomes associated with ctDNA clearance kinetics, tumor mutations, tumor mutational burden, circulating methylated DNA, tumor immune microenvironment profile, peripheral blood immune profile, and stool microbiome analyses. The enrollment period will be ̃12 mos. Pts will be followed for 18 mos following enrollment with ctDNA analysis at prespecified timepoints until imaging is positive for recurrence of disease or death. CT scans will be at 6-mo intervals. RFS will be determined in pts who clear ctDNA at 8 wks compared to those who do not. A single-stage design to test the null hypothesis that the 12-mo RFS is P≥0.20 versus the alternative (HA) that P≥0.35 has a sample size of 31 (alpha=0.151; power 0.811). If ≥9 of 31 pts (29%) are alive and recurrence-free at 12 mos, then gevokizumab will be considered promising for further study. Enrollment continues towards the primary endpoint. Clinical trial information: 05178576.