Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type
PMID
Authors L. Hwang, W. Wang, S. Qazi, K. Ng, O. D’cruz, V. Trieu
Title L-8 as a pharmacodynamic biomarker for TGF-b2 antisense (trabedersen) therapy: Results of a phase II trial
URL https://www.annalsofoncology.org/article/S0923-7534(20)37613-4/fulltext
Abstract Text Background: In a Phase I/II study of Trabedersen (OT-101), a phosphorothioate antisense specific for human TGF- b2 mRNA, patients with advanced pancreatic cancer (PAC) treated in the 2nd-line and beyond exhibited improved overall survival (OS) when OT-101 was followed with chemotherapy. Here, we examined the association between plasma levels of cyto-/chemokines and OS outcomes to identify potential biomarkers for improved OS. Methods: 37 PAC patients were treated with continuous IV infusion in escalating doses of 2 treatment schedules (7-days-on, 7-days-off and 4-days-on, 10-days-off). Plasma levels of 31 cyto-/chemokines were measured at 8 separate time points over 3 cycles of OT-101 treatment (140 mg/m2 /day, 4-days-on, 10-days-off). Standardized maximum levels of individual cyto-/chemokines on Day 2 were subtracted from levels on Day 5 of each cycle of treatment and correlated with log10 transformed OS values. Feedback interactions with PK parameters were also investigated utilizing an ANCOVA model. Results: A median OS of 14.5 months and 2.6 months was observed for 2nd-line patients treated with and without subsequent chemotherapies, respectively (p ¼ 0.0009). Increasing difference of IL-8 levels at Day 2 vs Day 5 was positively correlated with OS (R2 ¼ 0.58, P ¼ 0.0066). Stratifying for patients with and without chemo, R2 increased to 0.99 and 0.77 respectively. Similar results were observed for IL-15, with R2 ¼ 0.93 in patients with chemo and R2 ¼ 0.50 in those without. ANCOVA models for two PK parameters exhibited significant model fits (F3,7 ¼ 7.89, P ¼ 0.012 for Simulated Vz Mean; F3,7 ¼ 8.18, P ¼ 0.011 for Simulated Cl Mean) and the interaction effects resulted in lower p-values for the correlation of OS vs IL-8 levels. Conclusions: Increasing peak levels of IL-8 and IL-15 response on Day 2 of OT-101 treatment correlated with OS in PAC patients. This correlation with OS was evident regardless of subsequent chemotherapy or not indicating spikes in IL-8 and IL-15 as potential biomarkers for OT-101

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References