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 Display session 2

5927 - Phase 1b study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple negative breast cancer (NCT02474173).

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

Robert Wesolowski

Citation

Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242

Authors

R. Wesolowski1, A.M. Brufsky2, M. Chambers3, S. Bhattacharya4, M. Lustberg5, J.B. VanDeusen1, S. Sardesai1, N. Williams1, A.M. Noonan6, M. Phelps7, M. Grever8, J. Stephens9, W. Carson10, B. Ramaswamy1

Author affiliations

  • 1 Medical Oncology, Ohio State Univ Medical Center, 43210 - Columbus/US
  • 2 Medical Oncology, Magee-Womens Hospital of UPMC, 15213 - Pittsburgh/US
  • 3 Medical Oncology, University of Kentucky, 40536 - Lexington/US
  • 4 Medical Oncology, Thomas Jefferson University, 19107 - Philadelphia/US
  • 5 Clinic, The Ohio State Comprehensive Cancer Center, OH 43210 - Columbus/US
  • 6 Department Of Internal Medicine, Division Of Medical Oncology, The Ohio State University James Cancer Hospital, 43210 - Columbus/US
  • 7 Pharmacology, Ohio State Univ Medical Center, 43210 - Columbus/US
  • 8 Medical Oncology, Ohio State Univ Medical Center, 43210 - columbus/US
  • 9 Biostatistics, Ohio State Univ Medical Center, 43210 - columbus/US
  • 10 Surgical Oncology, Ohio State Univ Medical Center, 43210 - columbus/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 5927

Background

Heat shock protein 90 (HSP90) is a molecular chaperone required for proper folding and stabilization of proteins. Client proteins of HSP90 include many oncogenic proteins known to be over-activated in triple negative breast cancer (TNBC) such as AKT, EGFR and members of RAS/MAPK signaling pathway. Over-expression of HSP90 client proteins such as AKT and c-RAF has also been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent non-ansamycin small molecule inhibitor of HSP90.

Methods

Patients (pts) with inoperable or metastatic, TNBC were treated with onalespib and paclitaxel on days 1, 8, 15 every 28 days. Paclitaxel was given at a dose of 80 mg/m2 while the dose of onalespib was gradually increased from 120 mg/m2 to 260 mg/m2 in dose levels (DL) 1-4 using standard 3 + 3 design. In order to assess the effect of each drug on pharmacokinetics (PK) of the other drug, onalespib was given on day -7 prior to cycle 1 and skipped on day 1 of cycle 1. The primary objective was to determine dose limiting toxicities (DLT) and maximum tolerated dose (MTD). The secondary objectives were PKs of each agent, overall response rate (ORR), response duration and progression-free survival.

Results

20 pts were enrolled to dose escalation part (5, 3, 7 and 6 to DL 1-4 respectively). One pt in DL 1 did not start therapy due history of severe paclitaxel hypersensitivity and 2 pts (DL1 and DL 3) had to be replaced due to disease progression in cycle 1. One DLT occurred in 1 pt in DL3 (grade 3 nausea, vomiting and abdominal pain). No DLTs were noted in the highest DL testing onalespib at 260 mg/m2. The most common grade 3 or higher adverse events included diarrhea (55%), fatigue (55%), anemia (14%), leukopenia (24%) and neutropenia (41%). Diarrhea was self limiting, lasting 24-48 hrs post infusion and responded well to loperamide. ORR and clinical benefit rate in 16 evaluable pts was 25% and 62.5% respectively. Preliminary PK analysis showed no evidene of interaction between onalespib and paclitaxel.

Conclusions

Study regimen demonstrated acceptable safety profile. MTD of onalespib in combination with standard dose and schedule of paclitaxel was determined to be 260 mg/m2. Dose expansion study at MTD is currently ongoing.

Clinical trial identification

NCI 9876 (NCT02474173).

Editorial acknowledgement

Not applicable

Legal entity responsible for the study

Robert Wesolowski, MD.

Funding

Cancer Therapy Evaluation Program at the National Cancer Institute.

Disclosure

All 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
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.