Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion session - Gastrointestinal tumours, colorectal 1

5869 - Eltanexor (KPT-8602), a Second-Generation Selective Inhibitor of Nuclear Export (SINE) Compound, in Patients with Metastatic Colorectal Cancer (mCRC)

Date

20 Oct 2018

Session

Poster Discussion session - Gastrointestinal tumours, colorectal 1

Presenters

John Hays

Authors

J. Hays1, J. Zhang2, J.D. Berlin3, M. O'Hara4, M.A. Shah5, W. Reichmann6, W. Senapedis6, H. Achour6, E. Baloglu6, S. Shacham6, M. Kauffman6

Author affiliations

  • 1 Medical Oncology, Ohio State University, 43221 - Columbus/US
  • 2 Medical Oncology, Moffitt Comprehensive Cancer Center, Tampa/US
  • 3 Medicine, Vanderbilt Ingram Cancer Center, 37232-6307 - Nashville/US
  • 4 Medicine, University of Pennsylvania, 19104 - Philadelphia/US
  • 5 Department Of Medicine, Weill Cornell Medicine/ New York Presbyterian Hospital, New York/US
  • 6 Drug Discovery, Karyopharm Therapeutics, 02459 - Newton/US
More

Resources

Abstract 5869

Background

Overexpression of exportin 1 (XPO1) in malignant cells increases the nuclear export/inactivation of tumor suppressor proteins (e.g. p53, IκB), and promotes the translation of eIF4E-bound mRNAs coding oncoproteins (e.g. c-MYC, BCL-2, AR). Inhibition of XPO1 using selinexor, the first-in-human SINE compound, showed anticancer activity in patients (pts) with solid tumors including mCRC. Eltanexor (ELTA), a second-generation SINE compound, showed promising anticancer activity in preclinical models of CRC. Non-clinical and preliminary clinical activity of SINE compounds support the increased sensitivity in KRAS mutant neoplasia. Therefore, ELTA was evaluated in mCRC pts with known KRAS status.

Methods

This was part of a phase 1/2 study (NCT02649790)to determine the safety,preliminary efficacy, and recommended phase 2 dose of ELTA in pts with advanced cancers. Pts with mCRC (≥50% KRAS mutant) in expansion cohorts received once daily oral ELTAfor 5 days per week at 20 (n=7) or 30 (n=23) mg. Response was evaluated by RECIST 1.1 criteria every 28-day cycle.

Results

As of 15 Jul 2018, 23 pts with mCRC (of 30 pts; median prior therapies; 4 and age; 63) were evaluable for efficacy: 18 stable disease (SD; 1 pt with a 20% max tumor reduction) and 5 progressive disease (PD) after 1 mo, with no objective responses. Duration of treatment showed 30% (7/23) SD at 4 mos and 13% (3/23) SD at ≥6 mos. The preliminary median progression free survival (PFS) for all pts was 3.5 mos. The most common treatment-related adverse events (TRAEs) occurring in ≥20% of the population were vomiting (60%; 3% Gr≥3), nausea (50%; 7% Gr≥3), fatigue (40%; 17% Gr≥3), anorexia (30%; no Gr≥3), anemia (27%; 17% Gr≥3), hyponatremia (27%; 23% Gr≥3), and thrombocytopenia (23%; 7% Gr≥3 including the only Gr 4 TRAE observed in mCRC). There was no difference in sensitivity of KRAS wild type or mutant pts.

Conclusions

ELTA is well-tolerated with manageable AEs in mCRC. Even though this was small sample size, ELTA shows promise with a longer median PFS in this heavily treated population when compared to the currently available 3rdline therapies. Enrollment is complete with plans to initiate Phase 2/3 in late 2019.

Clinical trial identification

NCT02649790

Editorial Acknowledgement

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings