419O - Efficacy and safety of ceritinib in patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) and baseline brain metastases (BM)...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Thoracic cancers
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Tony Mok
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors K. Park1, D. Tan2, M.A. Ahn3, C. Yu4, C. Tsai5, T. Hida6, M. Nishio7, F. Branle8, C. Emeremni9, T. Mok10
  • 1Div Of Hem/onc, Dept Of Med, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 2Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 3Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul/KR
  • 4Department Of Internal Medicine, National Taiwan University, Taipei/TW
  • 5Department Of Chest Medicine, Taipei Veterans General Hospital, Taipei/TW
  • 6Department Of Thoracic Oncology, Aichi Cancer Center Hospital, 464–8681 - Nagoya/JP
  • 7Department Of Thoracic Medical Oncology, Japanese Foundation for Cancer Research, Tokyo/JP
  • 8Oncology Clinical Development, Novartis Pharma AG, Basel/CH
  • 9Biometrics And Data Management, Novartis Pharma AG, East Hanover/US
  • 10Department Of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong/CN

Abstract

Aim/Background

Ceritinib showed clinical activity in pts with ALK+ NSCLC in the ASCEND-2 and ASCEND-3 studies, with disease control rates (95% CI) of 77% (69.3, 83.8) and 90% (82.7, 94.3), respectively. Here we report safety data and summarize recently presented efficacy data for ALK+ NSCLC patients with baseline BM from these studies (ASCEND-2: ASCO 2015, Ab 8059 and ASCEND-3: ASCO 2015, Ab 8060).

Methods

Both single-arm, open-label, multicenter Ph 2 studies enrolled pts with ALK+ NSCLC and allowed pts with symptomatic, neurologically stable BM. All ASCEND-2 pts had received chemotherapy and crizotinib (CRZ) as their last treatment prior to ceritinib, with progression on CRZ or ≤30 days after last CRZ treatment. All but 2 pts in ASCEND-3 had received prior chemotherapy and all were ALK inhibitor-naïve. All pts received oral ceritinib 750 mg/d. Whole body and intracranial responses were assessed by investigator and a Blinded Independent Review Committee.

Results

At baseline 100/140 pts had BM in ASCEND-2 and 50/124 in ASCEND-3. 28% and 46%, respectively, had no prior brain radiation. Median durations of follow-up (range) were 11.2 (0.2–18.9) and 7.5 (0.6–13.8) mos, respectively. Table 1 shows efficacy. The most common AEs (any grade, regardless of study drug relationship) in pts with BM in ASCEND-2 & ASCEND-3 were nausea (82% & 78%), diarrhea (82% & 76%), and vomiting (64% & 72%), respectively. The majority of these were Grade1/2 and were managed with recommended dose adjustments. The most common grade 3/4 AEs were ALT increase (18% & 14%) and GGT increase (10% & 18%), respectively. In pts with BM, reports of an AE as the primary reason for study drug discontinuation was similar in frequency to those in the overall pt populations (ASCO 2015, abs 8059 & 8060).

ASCEND-2 ASCEND-3
Data cut-off 13 August 2014 27 June 2014
Investigator Review BIRC Investigator Review BIRC
Whole body responses in all pts with BM at baseline
(n = 100) (n = 100) (n = 50) (n = 50)
Overall response rate, n (%) [95% CI] 33 (33.0) [23.9, 43.1] 32 (32.0) [23.0, 42.1] 29 (58.0) [43.2, 71.8] 30 (60.0) [47.4, 71.7]
Disease control rate, n (%) [95% CI] 74 (74.0) [64.3, 82.3] 64 (64.0) [53.8, 73.4] 43 (86.0) [73.3, 94.2] 39 (78.0) [64.0, 88.5]
Median duration of responsea, mos [95% CI] 9.2 [5.5, 11.1] 9.3 [5.5, 12.9] 9.1 [7.5, NE] 9.4 [5.6, NE]
Median progression-free survival, mos [95% CI] 5.4 [4.7, 7.2] 6.8 [5.4, 7.4] 10.8 [7.3, NE]b 11.0 [7.2, NE]b
Intracranial responses in pts with active BM lesions selected as target lesionsc
(n = 20) (n = 33) (n = 10) (n = 17)
Overall intracranial response rate, n (%) [95% CI] 9 (45.0) [23.1, 68.5] 13 (39.4) [22.9, 57.9] 2 (20.0) [2.5, 55.6] 10 (58.8) [32.9, 81.6]
Intracranial disease control rate, n (%) [95% CI] 16 (80.0) [56.3, 94.3] 28 (84.8) [68.1, 94.9] 8 (80.0) [44.4, 97.5] 14 (82.4) [56.6, 96.2]

BIRC, Blinded Independent Review Committee; CI, confidence interval; NE, note evaluable aDuration of response calculated for patients with confirmed complete or partial response bData are not yet mature in the overall patient population, with >50% patients still ongoing cSelection as an active, target lesion indicated the lesion was a new lesion or an existing lesion progressing following local therapy.

Conclusions

Pts with ALK+ NSCLC and baseline BM derived clinically meaningful benefits with similar safety and tolerability profiles compared with the overall pt population.

Clinical trial identification

ASCEND-2: NCT01685060 ASCEND-3: NCT01685138

Disclosure

K. Park: consulting/advisory role: Astellas, AstraZeneca, AVEO, Eli Lilly, Hanmi, BI, Clovis, Novartis, KHK, ONO, Roche; research funding: AstraZeneca. D. Tan: research grants: Novartis; advisory role: Novartis, Boehringer Ingelheim, Pfizer. M.-J. Ahn: Advisory board: AstraZeneca, Boehringer Ingelheim. C.-M. Tsai: honoraria: AstraZeneca, Roche, Eli Lilly, BI, Pfizer, MSD; consulting/advisory role: AstraZeneca, Roche, Eli Lilly, BI, Pfizer Research funding: AstraZeneca. T. Hida: honoraria: Chugai, Pfizer Research funding: Chugai, Pfizer, Novartis. M. Nishio: consulting/advisor/speaker's bureau/research funding: AZ, BMS Japan, Chugai Pharmaceutical, Daiichi Sankyo Healthcare, Elekta, Eli Lily, Nichirei Biosciences, Novartis, Ono Pharmaceutical, Pfizer, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical. F. Branle, C. Emeremni: employee of Novartis Pharma AG. T. Mok: honoraria/consulting/advisor/speaker's bureau: Amgen, AstraZeneca, BI, BioMartin, Clovis Oncology, Eli Lilly, GSK, Janssen, Pfizer, Roche/Genentech, Merck, MSD, Novartis, Serono, SFJ Pharmaceutical. All other authors have declared no conflicts of interest.