1423O - Randomized phase 2 study of investigational aurora A kinase (AAK) inhibitor alisertib (MLN8237) + paclitaxel (P) vs placebo + P as second line ther...

Date 07 October 2016
Event ESMO 2016 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Small-Cell Lung Cancer
Presenter Taofeek Owonikoko
Citation Annals of Oncology (2016) 27 (6): 493-496. 10.1093/annonc/mdw389
Authors T.K. Owonikoko1, K. Nackaerts2, T. Csoszi3, G. Ostoros4, C. Baik5, Z. Mark6, E. Sheldon-Waniga7, D. Huebner8, E..J. Leonard9, D.R. Spigel10
  • 1Hematology/medical Oncology, Emory University, 30345 - Atlanta/US
  • 2Respiratory Diseases, Respiratory Oncology Unit, KU Leuven, University Hospitals Leuven, 3000 - Leuven/BE
  • 3Onkologiai Kozpont, Hetenyi G Korhaz, 5004 - Szolnok/HU
  • 4Viii. Tudobelosztaly, Orszagos Koranyi TBC es Pulmonologiai Intezet, 1121 - Budapest/HU
  • 5Thoracic/head And Neck Oncology, University of Washington Seattle Cancer Care Alliance, 98109 - Seattle/US
  • 63th, Tudogyogyintezet Torokbalint, 2045 - Törökbálint/HU
  • 7Oncology Statistics, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 02139 - Cambridge/US
  • 8Oncology Clinical Research, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 02139 - Cambridge/US
  • 9Clinical Science, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 02139 - Cambridge/US
  • 10Sarah Cannon Research Institute, Tennessee Oncology, 37203 - Nashville/US

Abstract

Background

Alisertib, a selective AAK inhibitor, showed single-agent antitumor activity in preclinical in vivo SCLC models and was synergistic with P in this setting. We report the efficacy (PFS, OS, ORR) and safety from this study.

Methods

Pts ≥18 y with SCLC relapsed

Results

178 pts were randomized (89/89) Arm A/B; median age 62/62 y. The analysis of PFS using IVRS stratification favored Arm A (median 101 vs 66 d) with HR 0.77; 95% CI 0.557, 1.067; p = 0.113. The analysis for PFS using the corrected stratification factors again favored Arm A with HR 0.72; 95% CI 0.522, 1.004; p = 0.038. Median OS was 186 vs 165 d, with HR 0.93; 95% CI 0.652, 1.341; p = 0.714 and ORR was 22% vs 18%, disease control rate 58% vs 46%, stable disease 55% vs 49%, and progressive disease 15% vs 26%. Pts received a median of 3 (1–9) vs 2 (1–11) cycles. Rates of AEs were higher in Arm A.

Safety population

Arm A (n = 87) Arm B (n = 89)
AE (≥20%) % AE (≥20%) %
Diarrhea 59 Nausea 34
Neutropenia 49 Fatigue 33
Anemia 44 Constipation 24
Fatigue 44 Vomiting 24
Nausea 33  ↓  Appetite 21
Stomatitis 33 Dyspnea 21
↓ Appetite 33 Anemia 20
Vomiting 32 Diarrhea 20
Dyspnea 24
Cough 20
Grade ≥3 AE 76% Grade ≥3 AE 51%
Drug-related Grade ≥3 AEs 67% Drug-related Grade ≥3 AEs 25%
Drug-related serious AEs 32% Drug-related serious AEs 7%
AEs leading to treatment discontinuation 15% AEs leading to treatment discontinuation 6%

Conclusions

Alisertib + P shows favorable PFS over placebo + P with both corrected and IVRS stratification. A similar favorable trend was observed for OS and ORR. The alisertib + P arm showed higher rates of AEs and discontinuation due to AEs. Further analyses are pending.

Clinical trial identification

NCT02038647; EudraCT 2013-003713-18 (Clinical Trial Protocol C14018 Protocol Amend 2 2015-01-23)

Legal entity responsible for the study

Millennium Pharmaceuticals, Inc.

Funding

Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Disclosure

T.K. Owonikoko: Consulting: Medivation, Novartis, Lilly, Amgen; Research funding: Novartis, Stemcentrix, BMS, Celgene, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Calithera, AbbVie. E. Sheldon-Waniga, D. Huebner: Employment (Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited). E.J. Leonard: Employment (Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited); stock ownership: Takeda Pharmaceutical Company Limited; Corporate-sponsored research: Takeda-sponsored clinical trial. All other authors have declared no conflicts of interest.