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2019 ASCO Annual Meeting!


Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)

Type: Poster Session

Time: Saturday June 1, 8:00 AM to 11:00 AM

Location: Hall A

Baseline cfDNA characteristics and evolution of cfDNA profile during treatment with selective FGFR inhibitor TAS-120.

Sub-category:
Circulating Biomarkers

Category:
Developmental Therapeutics and Tumor Biology (Nonimmuno)

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3056

Poster Board Number:
Poster Session (Board #48)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3056)

Author(s): Tyler J. Moss, Jordi Rodon Ahnert, Holly D. Oakley, Michael Kahle, Daniel D. Karp, Shubham Pant, Jeena Jacob, Victoria M. Raymond, Richard B. Lanman, Lawrence Kwong, Mark Routbort, Nital Soni, Jerry Huang, Milind M. Javle, Funda Meric-Bernstam; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Texas MD Anderson Cancer Center, Houston, TX; Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, TX; Guardant Health, Inc., Redwood City, CA; Taiho Oncology, Princeton, NJ; Taiho Oncology, Inc., Princeton, NJ

Abstract Disclosures

Abstract:

Background: There is an increasing role for cfDNA in monitoring response and mechanisms of resistance. We performed cfDNA analysis in a subset of patients enrolled on a Phase I trial with an irreversible, selective FGFR1-4 inhibitor, TAS-120. Methods: 58 plasma samples from 17 patients (13 with cholangiocarcinoma) were analyzed on a 73-gene, next-generation sequencing panel. Selected patients(pts) had longitudinal samples. Results: At least one alteration was detected in 46 cfDNA samples, in 16 (94%) of 17 pts – a pt with GBM had no alterations detected. 14 pts had alterations in FGFR2/3 by genomic testing of archival tumor samples, comprising 20 total alterations (18 unique). 10 of 20 FGFR2/3 alterations were also detected by cfDNA testing: 4/5 SNVs, 1/2 amplifications, 5/13 fusions. Three pts had FGFR/FGF alterations not included (thus not detected) in the cfDNA panel: 2 with FGF ligand amplification, and one FGFR4 mutation. 6 pts (35%) had PR, 5 (29%) had SD and 6 (35%) PD as a best response to TAS-120. Four pts had prior FGFRi: 2 had a PR, 1 SD, and 1 PD on TAS-120. Baseline cfDNA mutations became undetectable during treatment in 4/6 pts with PR. 4 of 6 PD pts had other driver mutations at baseline including mutations in PIK3CA, KRAS, IDH1, BRCA2, or amplifications in PIK3CA,PDGFR. 9 pts with cfDNA available at progression after SD/PR: 3 had acquired FGFR2 mutations (one each of V564L, V564F, or N549K). Two also acquired alterations in other candidate resistance genes (PTEN and MAP2K1). Another pt had low variant allele frequency (VAF) NRAS G12D and BRAF A694T pretreatment and had SD. At progression, cfDNA revealed an increase in NRAS VAF and mutations acquired in the MAPK pathway. One pt with prior FGFRi acquired FGFR2 V564I and V564K detected by cfDNA prior to initiation of TAS-120, and had a PR on TAS-120. There was a drop in FGFR2 V564I VAF with response that subsequently increased with progression. The patient also acquired a FGFR2 V564L mutation at progression. Conclusions:FGFR alterations can be detected by cfDNA. cfDNA may detect potential resistance mechanisms, including PI3K or MAPK pathway alterations and acquired FGFR2 mutations. Patients with gatekeeper mutations in cfDNA at baseline may still respond to TAS-120. Further study is needed to determine the impact of FGFR2 mutations and co-alterations on TAS-120 sensitivity.

 
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Meeting: 2019 ASCO Annual Meeting Abstract No: 3018 First Author: Alessandro Leal
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

2. Multimodality liquid biopsy for early monitoring and outcome prediction in first-line metastatic HER2-negative breast cancer: Final results of the prospective cohort from the French Breast Cancer InterGroup Unicancer (UCBG)— COMET study.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3019 First Author: Jean-Yves Pierga
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3. Circulating androgen receptor (AR) gene amplification and resistance to 177Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of a phase II clinical trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3020 First Author: Ugo De Giorgi
Category: Developmental Therapeutics and Tumor Biology (Nonimmuno) - Circulating Biomarkers

 

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