246 - Exploratory Analysis of ctDNA and Imaging Response in the Phase I/II CHORUS Study of Canakinumab with Chemoradiation and Durvalumab Consolidation for Stage III NSCLC

N. Shaverdian¹, M. Offin², K. Charalambous³, D. Gelblum¹, F. Santini³, L. A. Boe³, A. F. Shepherd¹, R. M. Gewanter¹, J. Y. Shin¹, A. Rimner¹, M. G. Kris⁴, I. Preeshagul², P. Paik², J. Eng², A. Iqbal², K. Ng², R. Shah³, M. Berger⁵, D. R. Gomez¹, and J. Chaft⁶; ¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ³Memorial Sloan Kettering, New York City, NY, ⁴Memorial Sloan Kettering Cancer Center, New York, NY, ⁵Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, ⁶Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

Purpose/Objective(s): Canakinumab is an anti–IL-1ß antibody that is hypothesized to inhibit protumor inflammation. The CHORUS study tested the efficacy of canakinumab with chemoradiation (cCRT + cana) and consolidation durvalumab (durva + cana) in patients with stage III NSCLC. The primary PFS endpoint is immature. Here, we report an exploratory analysis on circulating tumor DNA (ctDNA) kinetics and imaging response, hypothesizing that associations between both may best predict disease control. Materials/

Methods: This phase I/II trial enrolled 32 patients with stage III NSCLC, treated with canakinumab (200mg every 3 weeks, total of 15 cycles) with standard platinum-based cCRT and durvalumab consolidation. Plasma for ctDNA was analyzed at baseline, weeks 3 (On-Tx1), 7 (On-Tx2) and 16 (On-Tx3) using MSK-ACCESS, a cfDNA assay designed to detect alterations in 129 genes. Patients with matched tumor tissue (n=24) also underwent sequencing with MSK-IMPACT. Initial surveillance imaging was done 4 weeks post cCRT + cana, after which imaging was every 3 months. Response is per RECIST 1.1 criteria.
Results: Between June 2021 and April 2023, 32 patients received cCRT + cana and at least 1 cycle of durva + cana. Median age was 70 years, most patients (n=22, 69%) had stage IIIB/IIIC disease, adenocarcinoma histology (n=19, 59%), were female (n=18, 56%) and had a smoking histology (n=28, 88%). PDL1-TPS was available for 29 patients (91%) of which 14 (48%) were PDL1 <1%, 7 (24%) were PDL1 =1% to <50%, and 8 (28%) were PDL1 = 50%. Median follow-up for all patients was 11.2 months (IQR 8.2-21.1). On initial imaging 4 weeks post cCRT + cana, 23 patients (72%) had a PR/CR, 8 had SD (25%) and 1 was non-evaluable. With 11.2 months of follow-up, 26 patients (81%) had a CR/PR as the best overall response to therapy and 8 patients had confirmed PD. At baseline, all patients (n=32) had detectable ctDNA. Among patients who also underwent tissue based MSK-IMPACT (n=24), at baseline, 22 patients (92%) had at least one plasma alteration detected on MSK-ACCESS also detected in tumor tissue. On-Tx1 samples were assessed in 30 patients, of which 10 (33%) had undetectable ctDNA. All 10 patients (100%) with undetectable ctDNA at On-Tx1 had a PR/CR on initial imaging vs patients with detectable ctDNA at On-Tx1 (n=20) of whom 12 (60%) had a PR/CR on initial imaging (P=0.029). On-Tx3 samples were assessed in 29 patients of which 20 (69%) had undetectable ctDNA. Among patients with undetectable ctDNA (n=20) at On-Tx3, 18 (90%) showed a PR/CR as best overall response, and 3 (15%) developed subsequent PD. Among patients with detectable ctDNA (n=9) at On-Tx3, 6 (67%) showed a PR/CR and 3 (33%) showed SD as best overall response, and subsequently 4 (44%) developed PD. Among patients with both detectable ctDNA at On-Tx3 and best response of SD (n=3), all (100%) had subsequent PD.
Conclusion: Initial imaging response rate to cCRT + cana is encouraging. A combination of both ctDNA dynamics and imaging response appears promising to predict disease control.