Abstract 1423O
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.
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