6P - Circulating tumor DNA (ctDNA) next generation sequencing (NGS): Molecular prescreening for tailoring treatment in clinical trials

Background

CtDNA NGS analysis has the potential to identify patients (pts) with the appropriate genomic alterations for enrollment in clinical trials (CT), helping overcome the challenge of tissue biopsies.

Methods

Guardant360™ (G360) was performed in patients (pts) with colorectal, cholangiocarcinoma, thyroid, salivary gland, pancreatic cancer and treatment-naïve NSCLC who were candidates for clinical trials at Vall d’Hebron Institute of Oncology. Pts with an available tumor tissue sample of less than 6 months, those with a previously known tier 1 variant according to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) or known resistance mutations were excluded. Genomic alteration actionability was classified according to ESCAT. Our main objective was to analyze the targetable genomic alterations detected from all informative G360 tests, and evaluate pts inclusion in CT.

Results

108 patients were included from November 2019 to April 2021. G360 was informative in 96 pts (88.88%), and 36 pts (33.3%) had a previous tissue NGS result. Median Turn Around Time (TAT) for G360 was 8.5 days (7-15). Potentially targetable alterations were identified in 14 pts (14.58%); 5 pts (4.16%) with tier I variants and 9 pts (9.37%) with tier II variants. The main druggable alterations include: ERBB2 amplification (3), KRAS G12C mutation (mut) (3), ERBB2 exon 2 insertion (2), BRAF V600E mut (1), MSI-High (1), EGFR L858R mut (1), EGFR exon 20 indel (1), ERBB2 R678Q (1) and RET M918T mut (1). 5 pts (5.20%) received treatment based on the G360 report. 4/5 pts were treated in a clinical trial, and 3 pts achieved a partial response. We identified 46 tier III variants that could be potential targets in phase I trials. Moreover, 22/52 pts (42,30%) with CRC showed RAS-resistant mutations to anti-EGFR therapies. Table: 6P

Conclusions

G360 has a short turnaround time and is able to identify targetable alterations in patients with unknown genomic drivers. NGS of ctDNA can optimize clinical trial recruitment.

Legal entity responsible for the study

The authors.

Funding

Guardant Health Inc.

Disclosure

H. Verdaguer: Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Other, Travel grants: Amgen; Financial Interests, Personal, Other, Travel grants: Celgene; Financial Interests, Personal, Other, Travel grants: Ipsen; Financial Interests, Personal, Other, Travel grants: Servier. A. Callejo Perez: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: F. Hofmann-La Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Kyowa Kirin; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Leo Pharma; Financial Interests, Personal, Advisory Board: Medscape; Financial Interests, Personal, Advisory Board: Kern Pharma. I. Brana: Financial Interests, Personal, Advisory Board: Merck Sharp & Dome; Financial Interests, Personal, Advisory Board: Rakuten Medical; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Achilles Therapeutics; Financial Interests, Personal, Advisory Board: eTheRNA Immunotherapies; Financial Interests, Personal, Advisory Board: Cancer Expert Now; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Gliknik; Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: Kura Oncology; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Orion Pharma GmbH; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Shattuck Labs; Financial Interests, Personal, Research Grant: Nanobiotix; Financial Interests, Personal, Other, Travel grants: Seattle Genetics; Financial Interests, Personal, Other, Travel grants: AstraZeneca; Financial Interests, Personal, Other, Travel grants: Merck Serono. I. Baraibar Argota: Financial Interests, Personal, Other, Travel grants: Merck; Financial Interests, Personal, Other, Travel grants: Amgen; Financial Interests, Personal, Other, Travel grants: Sanofi. P. Iranzo Gomez: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: F. Hofmann-La Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Rovi; Financial Interests, Personal, Advisory Board: Kyowa Kirin; Financial Interests, Personal, Advisory Board: Grunenthal Pharma S.A.; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Medscape; Financial Interests, Personal, Advisory Board: Kern Pharma. F. Salva Ballabrera: Financial Interests, Personal, Research Grant, Travel grants: F. Hoffman La-Roche; Financial Interests, Personal, Research Grant, Travel grants: Sanofi-Aventis; Financial Interests, Personal, Research Grant, Travel grants: Amgen; Financial Interests, Personal, Research Grant, Travel grants: Merck Serono; Financial Interests, Personal, Research Grant, Travel grants: Servier; Financial Interests, Personal, Research Grant, Travel grants: Bristol Myers Squibb. M. Vieito Villar: Financial Interests, Personal, Advisory Board: Debio; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: TFS; Financial Interests, Personal, Other, Travel grants: Merck Serono; Financial Interests, Personal, Other, Travel grants: Roche. I. Faull: Financial Interests, Personal, Full or part-time Employment: Guardant Health Inc. J. Tabernero: Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Avvinity; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Chugai; Financial Interests, Personal, Advisory Board: Daichi Sankyo; Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Board: Genentech Inc.; Financial Interests, Personal, Advisory Board: HalloDX SAS; Financial Interests, Personal, Advisory Board: Hutchison MediPharma Internacional; Financial Interests, Personal, Advisory Board: Ikena Oncology; Financial Interests, Personal, Advisory Board: IQVIA; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Merus; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Neophore; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Orion Biotechnology; Financial Interests, Personal, Advisory Board: Peptomyc; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Samsung Bioepis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Tessa Therapeutics; Financial Interests, Personal, Advisory Board: Theramyc; Financial Interests, Personal, Expert Testimony: Imedex; Financial Interests, Personal, Expert Testimony: Medscape Education; Financial Interests, Personal, Expert Testimony: MJH Life Science; Financial Interests, Personal, Expert Testimony: PeerView Institute for Medical Education; Financial Interests, Personal, Expert Testimony: Physicians Education Resource (PER); Financial Interests, Personal, Research Grant: Amgen Inc.; Financial Interests, Personal, Research Grant: Array Biopharma Inc.; Financial Interests, Personal, Research Grant: AstraZeneca Pharmaceuticals LP; Financial Interests, Personal, Research Grant: BeiGene; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Debiopharm International SA; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Research Grant: Genentech Inc; Financial Interests, Personal, Research Grant: HalioDX SAS; Financial Interests, Personal, Research Grant: Hutchinson MediPharma International; Financial Interests, Personal, Research Grant: Janssen-Cilag SA; Financial Interests, Personal, Research Grant: MedImmune; Financial Interests, Personal, Research Grant: Menarini; Financial Interests, Personal, Research Grant: Merck Health KGaA; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merus NV; Financial Interests, Personal, Research Grant: Mirati; Financial Interests, Personal, Research Grant: Novartis Farmaceutica SA; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: PharmaMar; Financial Interests, Personal, Research Grant: Sanofi-Aventis Recherche & Développement; Financial Interests, Personal, Research Grant: Servier; Financial Interests, Personal, Research Grant: Taiho Pharma USA Inc; Financial Interests, Personal, Research Grant: Spanish Association Against Cancer Scientific Foundation; Financial Interests, Personal, Research Grant: Cancer Research UK. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BerGenBio; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Blueprint Medicine; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Meyers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Medscape; Financial Interests, Personal, Advisory Board: Merck KGaA; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Prime Oncology; Financial Interests, Personal, Advisory Board: Peptomyc; Financial Interests, Personal, Advisory Board: Peervoice; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Syneos Health; Financial Interests, Personal, Advisory Board: Springer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Samsung; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Touchtime; Financial Interests, Personal, Advisory Board: Grifols; Financial Interests, Personal, Research Grant: Fundación Merck Salud; Financial Interests, Personal, Research Grant: Oncology Innovation EMD Serono. E. Elez: Financial Interests, Personal, Advisory Board: F. Hoffman La-Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Array Pharmaceuticals; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Research Grant: F. Hoffman La-Roche; Financial Interests, Personal, Research Grant: MedImmune; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Pierre Fabre; Financial Interests, Personal, Research Grant: Sanofi-Aventis. T. Macarulla Mercade: Financial Interests, Personal, Advisory Board: Sanofi-Aventis; Financial Interests, Personal, Advisory Board: Shire; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Baxalta; Financial Interests, Personal, Advisory Board: QED Therapeutics; Financial Interests, Personal, Advisory Board: Baxter; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: Agios; Financial Interests, Personal, Research Grant: ASLAN Pharmaceuticals; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Halozyme; Financial Interests, Personal, Research Grant: Immunomedics; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Research Grant: Merrimack; Financial Interests, Personal, Research Grant: Millennium; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Novocure; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Pharmacyclics; Financial Interests, Personal, Other, Travel grants: Merck; Financial Interests, Personal, Other, Travel grants: H3 Biomedicine; Financial Interests, Personal, Other, Travel grants: Sanofi; Financial Interests, Personal, Other, Travel grants: Celgene; Financial Interests, Personal, Other, travel Grants: Servier. E. Garralda: Financial Interests, Personal, Advisory Board: F. Hoffman La-Roche; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Thermo Fisher Scientific; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: TFS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Thermo Fisher; Financial Interests, Personal, Research Grant: BeiGene. All other authors have declared no conflicts of interest.