99O - Phase 1/2 study of AP26113 in patients (Pts) with advanced malignancies, including anaplastic lymphoma kinase (ALK)-positive non-small cell lung can...

Date 17 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Rafael Rosell
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors R. Rosell1, S. Gettinger2, L.A. Bazhenova3, C.J. Langer4, R. Salgia5, K. Gold6, A.T. Shaw7, D.J. Dorer8, D. Kerstein9, D..R. Camidge10
  • 1Medical Oncology Service, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 2Thoracic Oncology Program, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 3Moores Cancer Center, University of California San Diego, San Diego/US
  • 4Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 5Thoracic Oncology, The University of Chicago Medical Centre, Chicago/US
  • 6Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 7Massachusetts General Hospital Cancer Center, Harvard Medical School, 02114 - Boston/US
  • 8Biostatistics, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 9Clinical Research, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 10Thoracic Oncology, University of Colorado Cancer Center, Aurora/US



AP26113, an investigational oral ALK inhibitor, has preclinical activity against native ALK and a broad range of crizotinib-resistant mutants. Results of a phase 1/2 study of AP26113 in pts with advanced malignancies guided dose selection for an ongoing pivotal phase 2 study in pts with ALK+ NSCLC (ALTA: ALK in Lung Cancer Trial of AP26113). We present findings from the phase 1/2 study, including ALK+ NSCLC pts, at dose levels considered for testing in the ALTA trial.


This single-arm, multicenter study evaluated AP26113 at total daily doses of 30–300 mg in pts with advanced malignancies (NCT01449461). This analysis evaluates safety of AP26113 at daily doses of 90 mg, 90 mg escalating to 180 mg after 7 days (90–180 mg), or 180 mg (including 90 mg bid), and efficacy in ALK+ NSCLC pts at these doses.


As of 4 Aug 2014, 137 pts had enrolled, 79 with ALK+ NSCLC (71/79 [90%] received prior crizotinib). Accrual in the cohorts of focus: 90 mg (n = 18), 90–180 mg (n = 32), and 180 mg (n = 48, including 4 pts dosed at 90 mg bid). Across the selected cohorts, the most common adverse events (AEs) were nausea (43%), diarrhea (34%), and fatigue (30%), mostly grade 1 or 2; the most common grade ≥3 AEs were increased lipase (6%), neoplasm progression (6%), and increased amylase (5%). Early-onset pulmonary symptoms were observed in 4% (2/50) of pts who started at 90 mg qd (0/32 in the 90–180 mg cohort) and 14% (6/44) who received 180 mg qd. The table shows responses in evaluable ALK+ NSCLC pts by selected dose cohorts.

Response in Evaluable ALK+ NSCLC Pts 90 mg Cohort (n = 9) 90–180 mg Cohort (n = 26)a 180 mg Cohortb (n = 25)
Overall response rate, n (%) 7 (78) 20 (77) 17 (68)
Complete response 0 2 (8) 1 (4)
Partial response 7 (78) 18 (69) 16 (64)
Stable disease 2 (22) 3 (12) 3 (12)
Progressive disease 0 1 (4) 5 (20)
Median PFS, wk (range) 51.7 (4.1-68.1) Not reached 47.1 (0.6-72.0)

PFS, progression-free survival.

a2 pts terminated prior to follow-up scan.

bIncludes pts in 180 mg qd (n = 23) and 90 mg bid (n = 2) cohorts


AP26113 was similarly active at daily doses of 90 mg and 180 mg in advanced ALK+ NSCLC pts. Early-onset pulmonary symptoms were less frequent in the 90 mg qd and 90–180 mg cohorts than in pts dosed at 180 mg qd. The AP26113 90 mg qd and 90–180 mg qd regimens are being evaluated in the phase 2 ALTA trial in ALK+ NSCLC pts resistant to crizotinib.

We acknowledge Glen Weiss, MD for his contributions to the study.


S. Gettinger: consultancy, research funding, & honoraria ARIAD

C.J. Langer: Research funding (ARIAD)

A.T. Shaw: Consultancy (ARIAD)

D.J. Dorer and D. Kerstein: Employment and equity ownership (ARIAD)

D.R. Camidge: Research funding & honoraria (ARIAD)

All other authors have declared no conflicts of interest.