Abstract 92P
Background
Next generation sequencing in tissue is limited by sample availability and turnaround time. Here, we present the first results of the CLIMB360 study, where we performed prospective and real-time sequencing of ctDNA across multiple metastatic cancer types.
Methods
We collected a single blood sample at least 10 days apart from last therapy and analyzed by Guardant360 plasma-based NGS standardized assay which covers microsatellite instability [MSI] and 74 genes. Alterations [A] were reported as pathogenic [P], variant of unknown significance [VUS] or synonymous alteration [SA]. We classified specific gene A reported based on OncoKB therapeutic levels of evidence [LE] and collected date of extraction and report. Pts with NSCLC were treatment naïve; pts with other cancer-types could be of any line of treatment.
Results
From 08/2019 to 02/2021 we analyzed blood samples from 321 patients (pts) with NSCLC (105 adenocarcinoma, 22 squamous, 13 other), pancreatic ductal adenocarcinoma (68), colorectal carcinoma (CRC) (45), cholangiocarcinoma (CHO)(40), breast (9), thyroid (7) and salivary gland carcinoma (9). Results were available in a median of 9.1 natural days (IQR 2) from extraction. In 89% (287) of pts, we identified >=1 genomic A, being most of the cases P (204, 63%). 28 out of the 74 genes were ranked as LE 1-2 by OncoKB. In 82 (25.5%) pts, >=1 specific P A was associated with LE 1-2 either in the same histology of the patient (34, 10.6%) or in a different one (48, 14.9%) which opens the opportunity for targeted drugs approved or within clinical trials. The remaining 122 P were not associated with LE 1-2. A total of 1239 gene A were detected, 802 P and 437 VUS/SA. 93 P had LE1-2 including 3 MSI high. Most of them were identified in NSCLC adenocarcinoma, CHO and CRC. Table: 92P
| LE 1-2 P A | NSCLC adenoca | Large NSCLC | Other NSCLC | Breast cancer | Cholangio | Colorectal adenoca | Salivary gland | Pancreatic adenoca | Squamous NSCLC | TOTAL GENE |
| MSI-H | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 3 |
| ALK | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| ATM | 6 | 0 | 0 | 0 | 3 | 2 | 0 | 3 | 0 | 14 |
| BRAF | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 |
| BRCA1 | 3 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 |
| BRCA2 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 3 |
| EGFR | 14 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 17 |
| ERBB2 | 3 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 6 |
| FGFR3 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 4 |
| IDH1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 4 |
| IDH2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 3 |
| JAK2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| MET | 4 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 5 |
| NF1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| PDGFRA | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| PIK3CA | 3 | 2 | 0 | 1 | 4 | 3 | 0 | 3 | 4 | 20 |
| RET | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| TOTAL HISTOLOGY | 42 | 2 | 1 | 4 | 16 | 13 | 1 | 7 | 7 | 93 |
Conclusions
Real-time and prospective genomic profiling of pts with advanced cancer using ctDNA is feasible, fast and helps to identify therapeutic targets approved or evaluated in clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Garcia-Corbacho: Financial Interests, Personal, Advisory Board, FGFR inhibitors implementation in clinical practice: Johnson and Johnson Pharmaceutical; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Johnson and Johnson Pharmaceutical; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Boehringer; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Astellas; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Cytomx; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Incyte; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Lilly; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Menarini; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Merck; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Bayer; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Amgen; Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Daichii Sankyo. I. Faull: Financial Interests, Personal, Member: Guardant. M.L. Campillo: Financial Interests, Personal, Member: Guardant. L. Mezquita: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Non-Financial Interests, Personal, Other: BMS. All other authors have declared no conflicts of interest.