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O21 - SCLC II (ID 119)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
O21.06 - MLN8237 (alisertib), a selective Aurora A Kinase (AAK) inhibitor, in patients with relapsed/refractory small cell lung cancer (SCLC): Phase 2 results (ID 2815)
16:15 - 17:45 | Author(s): P. Serwatowski
AAK, a key mitotic regulator, plays an important role in carcinogenesis. AAK is frequently overexpressed/amplified in a variety of human cancers. Inhibition of AAK has been associated with tumor inhibition in SCLC patients; thus, AAK is an attractive target in SCLC treatment. The investigational, oral, selective AAK inhibitor MLN8237 is under evaluation in patients with advanced hematologic and non-hematologic malignancies. A phase 1/2 study (NCT01045421) evaluated MLN8237 in patients with solid tumors; phase 2 data for the SCLC cohort are presented.
Patients aged ≥18 years with relapsed/refractory SCLC, ECOG PS 0–1, and ≤2 prior cytotoxic chemotherapy regimens were eligible (symptomatic and untreated brain metastases were excluded); sensitive and resistant/refractory was defined as recurrence > or ≤90 days of frontline therapy respectively. MLN8237 50 mg was administered twice-daily for 7 days (21-day cycles). Using a Simon’s optimal 2-stage design, ≥2 objective responses were required in the first 20 response-evaluable patients to proceed to the expansion stage. Primary objective: overall response rate (ORR) by RECIST v1.1. Secondary objectives: safety, duration of response (DOR), and progression-free survival (PFS). Exploratory studies included whole-exome sequencing in banked tumor specimens to identify genetic markers/mutated pathways associated with differential response.
As of April 2013, 60 patients were enrolled; median age, 62 years (range 43–76); median number of cycles 2 (range 1–15). 48 patients (80%) were response-evaluable (chemo-sensitive, n=36; chemo-refractory, n=12). Prior lines of therapy and efficacy data are shown in the table. ORR was 21%, median PFS 2.11 months. Most common grade ≥3 drug-related AE included neutropenia (53%) and febrile neutropenia (8%); all AEs were reversible.14 patients discontinued due to AEs (treatment-related in 3 patients: hyponatremia, thrombocytopenia, acute generalised exanthematous pustulosis; each, n=1). 13 on-study deaths were reported; none were considered drug-related (most frequent cause was disease progression [n=6]). Whole-exome sequencing of selected tumor samples was completed. Preliminary results will be presented.
MLN8237 has a generally manageable toxicity profile; data from this study suggests it has single agent antitumor activity in SCLC patients with sensitive or resistant-refractory relapse, supporting further evaluation of MLN8237 in different combination strategies in this tumor type.
* Numbers of events: 7; **Not enough events to give meaningful estimates.
All Chemo-sensitive Chemo-refractory Prior lines of therapy First line, n (%) N=48 n=36 n=12 Platinum/etoposide 45 (94) 33 (92) 12 (100) Other 3 (6) 3 (8) – Second line, n (%) N=23 n=19 n=4 Rechallenge 13 (57) 12 (63) 1 (25) Topotecan 3 (13) 2 (11) 1 (25) Other 7 (30) 5 (26) 2 (50) Efficacy data N=48 n=36 n=12 Median cycles (range) 2.5 (1–15) 3.5 (1–15) 2 (2–6) Best response, n (%) ORR (PR) 10 (21) 7 (19) 3 (25) SD 16 (33) 13 (36) 3 (25) PD 22 (46) 16 (44) 6 (50) Median DOR (months) 4.1* –** –** Median PFS (months) 2.11 2.58 1.74
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