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

ePoster Display

854P - Final results of a phase II study of tipifarnib in chronic myelomonocytic leukemia (CMML) and other myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

Date

16 Sep 2021

Session

ePoster Display

Presenters

Mrinal Patnaik

Citation

Annals of Oncology (2021) 32 (suppl_5): S773-S785. 10.1016/annonc/annonc676

Authors

M.M. Patnaik1, M.A. Sekeres2, A. DeZern3, S. Luger4, L. Sproat5, R. Bejar6, G. Hobbs7, G.J. Roboz8, M. Leoni9, B. Martell9, E. Padron10

Author affiliations

  • 1 Bone Marrow Transplant Program, Mayo Clinic, 55905 - Rochester/US
  • 2 Division Of Hematology, University of Miami, Miami/US
  • 3 Division Of Hematology Malignancies, Leukemia Program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore/US
  • 4 Division Of Hematology Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 5 Bone Marrow Transplant Program, Mayo Clinic, Phoenix/US
  • 6 Divisions Of Hematology-oncology And Bone Marrow Transplantation, UC San Diego Moores Cancer Center, San Diego/US
  • 7 Hematology/oncology, Massachusetts General Hospital, Boston/US
  • 8 Clinical And Translational Leukemia Program, Weill Cornell Medicine, New York/US
  • 9 Clinical Development, Kura Oncology, Boston/US
  • 10 Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa/US
More

Abstract 854P

Background

Tipifarnib is a potent and selective inhibitor of the enzyme farnesyltransferase (FT). While all RAS isoforms (KRAS/NRAS/HRAS) are FT substrates, only HRAS is exclusively dependent upon farnesylation for membrane localization and signaling activation. Oncogenic RAS pathway mutations (NRAS, KRAS, CBL, and PTPN11) are seen in ∼30% of patients (pts) with CMML and are associated with a proliferative phenotype and adverse outcomes. Initial findings suggested tipifarnib may have greater activity in pts with RAS wildtype (wt) CMML. Given these findings, we investigated the activity of tipifarnib in pts with CMML and other MDS/MPN with specific biomarkers of interest.

Methods

This Ph2 study (NCT02807272) is a single-arm, open-label trial investigating the anti-tumor activity of tipifarnib in pts with CMML and MDS/MPN. Pts received tipifarnib 400 mg administered orally twice daily on days 1-21 of 28-day treatment cycles until progression of disease or unacceptable toxicity. The primary objectives were to assess ORR per MDS/MPN IWG criteria in KRAS/NRAS wt and mutant CMML pts and to examine ORR in pts with MDS/MPN with high and low CXCR4/CXCR2 ratio in the bone marrow. Secondary objectives included safety and additional efficacy analyses.

Results

44 pts (37 CMML and 7 MDS/MPN) were treated with tipifarnib. All pts had at least one treatment-related adverse event (AE), and 15 (34%) pts had at least one treatment-related serious AE. Seven (16%) pts discontinued tipifarnib due to treatment-related AEs. There were no treatment-related deaths. The most frequently observed treatment-related AEs (all grades) were anemia, nausea, diarrhea, and fatigue. Thirty-two evaluable CMML pts were had an overall ORR of 21.9% (7/32). ORR was 14.3% (3/21) in KRAS/NRAS wt pts and 33.3% (3/9) in pts with KRAS and/or NRAS mutation; two pts had unknown KRAS/NRAS status. Four MDS/MPN evaluable pts had an ORR of 25%; sample size was too small to meaningfully evaluate CXCR4/CXCR2 ratio in these pts.

Conclusions

Overall, data from this Ph2 trial showed that in general, tipifarnib was reasonably well tolerated and demonstrated modest efficacy in a difficult-to-treat patient population with limited therapeutic options.

Clinical trial identification

NCT02807272.

Editorial acknowledgement

Legal entity responsible for the study

Kura Oncology.

Funding

Kura Oncology.

Disclosure

M.M. Patnaik: Financial Interests, Personal, Advisory Board: Kura Oncology. M.A. Sekeres: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Novartis. A. DeZern: Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AbbVie. S. Luger: Financial Interests, Personal, Advisory Role: Daichii-Sankyo; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Acceleron; Financial Interests, Personal, Advisory Role: Agios; Financial Interests, Personal, Advisory Role: Loxo Oncology; Financial Interests, Personal and Institutional, Research Grant: Onconova; Financial Interests, Personal and Institutional, Research Grant: Kura Oncology; Financial Interests, Personal and Institutional, Research Grant: F. Hoffmann-La Roche; Financial Interests, Personal and Institutional, Research Grant: Ariad; Financial Interests, Personal and Institutional, Research Grant: Biosight. R. Bejar: Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Astex; Financial Interests, Personal and Institutional, Research Grant: Takeda; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal, Stocks/Shares: Aptose Biosciences; Financial Interests, Personal, Full or part-time Employment: Aptose Biociences. G. Hobbs: Financial Interests, Personal and Institutional, Research Grant: Incyte; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Constellation; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Constellation; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: BMS/Celgene. G.J. Roboz: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Agios; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Amphivena Therapeutics; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Astex Pharmaceuticals; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Array BioPharma/Pfizer; Financial Interests, Personal, Advisory Role: Celator Pharmaceticals; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: CTI BioPharma; Financial Interests, Personal, Advisory Role: Genoptix; Financial Interests, Personal, Advisory Role: Immune Pharmaceuticals; Financial Interests, Personal, Advisory Role: Janssen Pharmaceuticals; Financial Interests, Personal, Advisory Role: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Role: Orsenix; Financial Interests, Personal, Advisory Role: Juno Therapeutics; Financial Interests, Personal, Advisory Role: MEI Pharma; Financial Interests, Personal, Advisory Role: MedImmune; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Onconova Therapeutics; Financial Interests, Personal, Advisory Role: Roche/Genetech; Financial Interests, Personal, Advisory Role: Sunesis; Financial Interests, Personal and Institutional, Research Grant: Celletis. M. Leoni, B. Martell: Financial Interests, Personal, Full or part-time Employment: Kura Oncology. E. Padron: Financial Interests, Personal and Institutional, Research Grant: Incyte; Financial Interests, Personal and Institutional, Research Grant: Kura Oncology; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal, Advisory Role: Stemline; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: Taiho. All other authors have declared no conflicts of interest.

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