Abstract 1735
Background
The previous analysis of phase 2, ASCEND-3 study (NCT01685138; data cutoff: November 15, 2015) demonstrated prolonged median progression-free survival (mPFS) with ceritinib 750 mg/d (fasted) in ALKi-naïve patients with ALK+ NSCLC, who had received ≤3 prior lines of chemotherapy. The current analysis (data cutoff: January 22, 2018) from ASCEND-3 study reports the final safety and efficacy results including overall survival (OS).
Methods
ASCEND-3 is a multicenter, single-arm, open-label, phase 2 study in ALKi-naïve patients (aged, ≥18 years) with locally advanced or metastatic ALK+ NSCLC, who had received ≤3 lines of chemotherapy. Patients received oral ceritinib 750 mg/d (fasted). Primary endpoint was overall response rate (ORR) per RECIST v1.1 (by investigator). Secondary endpoints were ORR (by blinded independent review committee [BIRC]); overall intracranial response rate (OIRR), duration of response (DOR), disease control rate (DCR), PFS (by investigator and BIRC); OS; and safety.
Results
Of 124 ceritinib-treated patients, 123 (99.2%) had received prior antineoplastic regimens (31 patients [25.0%], ≥3 regimens), and 49 (39.5%) had baseline brain metastases. Median follow-up time was 52.14 months (range, 48.4-60.1). Median duration of drug exposure was 23.2 months (range, 0.1-55.2). Median OS was 51.3 months (95% CI: 42.7, 55.3). Other efficacy results are shown in the table below. The most common adverse events (AEs [all grades], ≥60% of patients), suspected to be drug related, were diarrhea (83.1%), nausea (76.6%), and vomiting (69.4%). Grade 3/4 AEs suspected to be drug related were reported in 81 patients (65.3%). Overall, 18 patients (14.5%) had an AE leading to treatment discontinuation.
| Investigator Assessment (N* = 124) | BIRC Assessment (N* = 124) | |
| Overall response rate, n (%) (95% CI) | 84 (67.7) (58.8, 75.9) | 79 (63.7) (54.6, 72.2) |
| Disease control rate, n (%) (95% CI) | 112 (90.3) (83.7, 94.9) | 107 (86.3) (79.0, 91.8) |
|
Median duration of response (in responders), months (95% CI) | M‡ = 84 24.0 (14.8, 37.5) | M‡ = 79 27.3 (16.6, 44.3) |
| Median progression-free survival, months (95% CI) | 16.6 (11.0, 23.2) | 19.4 (10.9, 29.3) |
| *Total number of patients included in the full analysis set. ‡Total number of patients with confirmed complete response or partial response. | ||
Conclusions
Ceritinib demonstrated prolonged and clinically meaningful OS, PFS, and DOR in chemotherapy pretreated (≤3 lines), ALKi-naïve patients with ALK+ NSCLC. The safety profile is consistent with the previous studies.
Clinical trial identification
NCT01685138