Abstract 1236P
Background
ctDNA-Lung-Detect is a multi-centre investigator-initiated prospective study assessing circulating tumour DNA (ctDNA) detection and association with recurrence free survival in patients with early stage, resected non-small cell lung cancer (NSCLC) (NCT05254782). Herein, we describe a sub-population of non-shedding ctDNA tumours, to help identify patients who remain high risk of relapse and those who may benefit from treatment escalation.
Methods
Patients with clinical stage I (T1-2N0) or multifocal T3-4 <4cm N0 NSCLC planned for resection consented to plasma ctDNA assessment before and after surgery, and at 12 months post-resection or relapse using the tumour-informed RaDaR® assay.
Results
Between July 2021 and April 2024, 231 patients were enrolled; 138 patients have preoperative ctDNA results. In 76.1% (105/138), ctDNA was not detected pre-operatively. Non-shedding patients were less likely to be male vs female (OR 0.40; CI 95% 0.18, 0.89, p <0.05); Current smokers vs never smokers (OR 0.21; 0.06, 0.74, p <0.01); Tumours were less likely to have non-squamous histology (OR 0.08; 0.02, 0.26, p <0.0001); Less likely to be T3/4 vs T1 (OR 0.04; 0.01, 0.16, p <0.0001) and less likely to be node positive vs negative (OR 0.22; 0.07, 0.71, p <0.01). An identifiable driver mutation (EGFR, ALK, KRAS G12C, ROS1, RET, MET exon 14 skipping, BRAF V600E or ERBB2) was more likely to be present when ctDNA was not detected (OR 2.71; 1.11, 6.59, p <0.03) and tumours were less likely to be PD-L1 >50% compared to <1% (OR 0.22; 0.08, 0.65, p <0.006). Four patients recurred where ctDNA was not detected; all were female with adenocarcinomas; one was a never smoker, two were previous smokers and one was a current smoker; three were stage 1, one was stage 2, and all had driver mutations.
Conclusions
This study represents one of the largest prospective cohorts of ctDNA assessment in patients with early stage resected NSCLC. Non-shedding patients were less likely to be male, current smokers, have PD-L1 high tumours, and were more likely to have an identifiable driver mutation. As data matures, we will be able to characterize non-shedding patients whom are at high risk of relapse and offer personalized approaches to escalation of treatment.
Clinical trial identification
NCT05254782.
Editorial acknowledgement
Legal entity responsible for the study
University Health Network.
Funding
Ontario Institute for Cancer Research, Princess Margaret Cancer Foundation Grand Challenge, Neogenomics (RADAR assay).
Disclosure
C. Pipinikas, A. Chevalier: Financial Interests, Personal and Institutional, Financially compensated role: Neogenomics. All other authors have declared no conflicts of interest.
Resources from the same session
1074TiP - A phase I study of GIGA-564, a minimally blocking anti-CTLA-4 monoclonal antibody
Presenter: James Gulley
Session: Poster session 04
1075TiP - A phase I trial of ATG-101, an investigational PD-L1×4-1BB bispecific antibody, in patients with advanced solid tumors and mature B cell non-Hodgkin lymphomas: PROBE-CN
Presenter: Junli Xue
Session: Poster session 04
Resources:
Abstract
1083P - KEYMAKER 02B: A randomized trial of pembrolizumab (pembro) alone or with investigational agents as first-line treatment for advanced melanoma
Presenter: Reinhard Dummer
Session: Poster session 04
1084P - Phase II study of AI-designed personalized neoantigen cancer vaccine, EVX-01, in combination with pembrolizumab in advanced melanoma
Presenter: Muhammad Khattak
Session: Poster session 04
1085P - Adoptive cell therapy with TCR gene-engineered T cells directed against MAGE-C2-positive melanoma: An ongoing phase I trial
Presenter: Brigit van Dijk
Session: Poster session 04
1086P - Intratumoral (IT) administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+myeloid dendritic cells (myDC) with the immunologic adjuvant AS01B plus ipilimumab (IPI) and IV nivolumab (NIVO) in patients with refractory advanced melanoma: A phase Ib clinical trial
Presenter: Manon Vounckx
Session: Poster session 04
1087P - Phase II study of niraparib in patients with advanced melanoma with homologous recombination pathway gene mutations
Presenter: Kevin Kim
Session: Poster session 04
1088P - Molecular profiling and matched targeted therapy for patients with advanced melanoma: Results from part I of the MatchMEL study
Presenter: Andrea Boutros
Session: Poster session 04
1089P - Longitudinal biomarker analysis and outcomes for patients (pts) treated with neoadjuvant nivolumab (nivo) and relatlimab (rela) in surgically resectable melanoma
Presenter: Elizabeth Burton
Session: Poster session 04
Resources:
Abstract
1090P - High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma
Presenter: Lotte Hoeijmakers
Session: Poster session 04