Abstract 3317
Background
ctDNA allows monitoring of response to therapy and serves as a liquid biopsy for pt selection for targeted therapies. We used samples from pts with NSCLC enrolled in an ongoing phase I/Ib trial (NCT02099058) treated with telisotuzumab vedotin (ABBV-399; teliso-v) alone and in combination with erlotinib or nivolumab to assess the frequency of mutant alleles in ctDNA and the association between ctDNA levels and OR to teliso-v.
Methods
Plasma was collected pre- (C1D1) and post-treatment (≥C2D1) and analyzed using 64-gene PlasmaSELECT™ assay (PGDx). Correlations between ctDNA detection probability and best OR were assessed by Fisher’s exact test; if C2D1 samples were not available, C3D1 (if CR/PR/SD) or FV samples (if PD) were used. The sum of variant allele fraction for all somatic mutations (SumVAF) at C1D1 and C2D1 was compared between response groups and between matched C1D1 and C2D1 samples.
Results
109 pts were analyzed (C1D1 [n = 108]). Among 56 pts without variant alleles detected at C1D1, ctDNA detection probability at ≥C2D1 was similar regardless of response (P = 0.51). For 52 pts with ctDNA detectable at C1D1, ctDNA detection probability at ≥C2D1 was higher for SD/PD (85%) vs CR/PR (55%), but not significant (P = 0.15). For all response groups SumVAF decreased from C1D1 to C2D1, suggesting a pharmacodynamic effect of teliso-v. SumVAF was significantly lower in pts with CR/PR vs SD/PD at C1D1 (P = 0.015) and marginally lower at C2D1 (P = 0.097).Table:
1469P Pre- and post-treatment mean (stdev) sum of variant allele fraction by response category
CR/PR n = 24 | SD n = 58 | PD n = 27 | P§ (FC) of SumVAF: SD/PD vs CR/PR | |
---|---|---|---|---|
Pre-treatment (C1D1) n = 108* | 3% (6%) | 8% (15%) | 6% (15%) | 0.015 (2.88) |
Post-treatment (C2D1) n = 83† | 1% (5%) | 4% (7%) | 3% (9%) | 0.097 (2.87) |
P‡, C1D1 vs C2D1 Mean decrease of SumVAF from C1D1 to C2D1 | 0.01 2% | 0.04 3% | 0.02 4% |
C1D1 data, missing for 1 patient with SD.
†C2D1 data, missing for 26 patients (4 CR/PR, 11 SD, and 11 PD).
‡By pair-wise t-test on 82 patients with both C1D1 and C2D1 data available.
§By 2-group t-test.
C, cycle; CR, complete response; D, day; FC, fold change; PD, progressive disease; PR, partial response; SD, stable disease; stdev, standard deviation; SumVAF, sum of variant allele fraction for all somatic mutations.
Conclusions
Baseline SumVAF levels and ctDNA detection probability at ≥C2D1 were lower with CR/PR vs SD/PD in pts with detectable ctDNA at C1D1. SumVAF decreased by C2D1 regardless of response, with more consistent reduction in pts with CR/PR. These data may suggest that discrete patterns of change in SumVAF over time correlate with OR outcome. Further investigation is warranted to assess ctDNA’s predictive value.
Clinical trial identification
NCT02099058.
Editorial acknowledgement
Iratxe Abarrategui, PhD, CMPP, from Aptitude Health, The Hague, Netherlands; funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
R.S. Heist: Advisory / Consultancy: Apollomics; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Tarveda Therapeutics; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Peregrine Pharmaceuticals; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Debiopharm Group; Research grant / Funding (institution): Corvus Pharmeceuticals; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Pfizer. M. Motwani: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. L. Naumovski: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. J. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. B.A. Bach: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. X. Lu: Shareholder / Stockholder / Stock options, Full / Part-time employment: AbbVie. K. Kelly: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Regeneron; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: EMD Serono; Honoraria (self), Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Licensing / Royalties, web information resource : UpToDate; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Transgene; Research grant / Funding (institution): Lycera.
Resources from the same session
5823 - Pulmonary tumor-draining vein exosomal lincRNA-p21 levels impacts non-small cell lung cancer prognosis
Presenter: Joan Castellano
Session: Poster Display session 1
Resources:
Abstract
1842 - Immunological impact of surgery in NSCLC patients
Presenter: Akitoshi Yanagihara
Session: Poster Display session 1
Resources:
Abstract
4124 - The prognostic value of selected immunological panel in predicting the prognosis of early-stage resectable non-small cell lung cancer
Presenter: Sha Zhao
Session: Poster Display session 1
Resources:
Abstract
4468 - Genomic Heterogeneity and Clonality Analysis of Multiple synchronous lung cancers (MSLCs)
Presenter: Fachen Zhou
Session: Poster Display session 1
Resources:
Abstract
5547 - Analysis of immunosuppressive factors produced by tumorspheres in NSCLC. Prognostic value of Galectin-3 in adenocarcinoma
Presenter: Susana Torres Martinez
Session: Poster Display session 1
Resources:
Abstract
1658 - Frequency of epidermal growth factor receptor (EGFR) mutations in stage IB–IIIA EGFR mutation positive non-small-cell lung cancer (NSCLC) after complete tumour resection
Presenter: Masahiro Tsuboi
Session: Poster Display session 1
Resources:
Abstract
1535 - EGFR mutation is not a prognostic factor in completely resected lymph node–negative pulmonary adenocarcinoma (LNNPA)
Presenter: Nussara Leeladejkul
Session: Poster Display session 1
Resources:
Abstract
3262 - Prognostic significance of elements of the adaptive immunity in the microenvironment of early-stage non small cell lung cancer
Presenter: Aliki Liakea
Session: Poster Display session 1
Resources:
Abstract
4643 - Combined immunoscore for prognostic stratification of early stage NSCLC patients
Presenter: Giulia Pasello
Session: Poster Display session 1
Resources:
Abstract
4819 - Radiation-induced lung injury and misdiagnosis rate after SBRT
Presenter: Xiaolong Fu
Session: Poster Display session 1
Resources:
Abstract