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
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract