1292P - ALK inhibitor AP26113 in patients with advanced malignancies, including ALK+ non-small cell lung cancer (NSCLC): Updated efficacy and safety data

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Drug Development
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Scott Gettinger
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors S. Gettinger1, L. Bazhenova2, R. Salgia3, C. Langer4, K. Gold5, R. Rosell6, A. Shaw7, G.J. Weiss8, N.I. Narasimhan9, D.J. Dorer10, V. Rivera11, T. Clackson12, F.G. Haluska13, R. Camidge14
  • 1Thoracic Oncology Program, Yale University School of Medicine, 06510 - New Haven/US
  • 2Health Sciences, UCSD Moores Cancer Center, La Jolla/US
  • 3Department Of Medicine, Section Of Hematology/oncology, University of Chicago, Chicago/US
  • 4Abramson Cancer Center, University of Pennsylvania, Philadelphia/US
  • 5Cancer Center, MD Anderson, Houston/US
  • 6Medical Oncology Service, Instituto Oncologico Dr Rosell, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 7Hematology/oncology, Massachusetts General Hospital, Boston/US
  • 8Virginia G. Piper Cancer Center Clinical Trials, Scottsdale Healthcare, 85258 - Scottsdale/US
  • 9Dmpk, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 10Biostatistics, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 11Preclinical & Translational Research, ARIAD Pharmaceuticals, 02139 - Cambridge/US
  • 12Research & Development, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 13Clinical Research & Development, ARIAD Pharmaceuticals, Inc., Cambridge/US
  • 14Division Of Medical Oncology, University of Colorado, Denver/US

Abstract

Aim

AP26113 is an investigational orally-active tyrosine kinase inhibitor with preclinical activity against ALK and all 9 clinically-identified crizotinib-resistant mutants tested.

Methods

The Phase (Ph) 2 portion of a Ph1/2 single arm, multicenter study in patients (pts) with advanced malignancies is underway. We report updated safety for all treated pts and efficacy data for ALK+ NSCLC pts previously treated with crizotinib. NCT01449461.

Results

As of 17 March 2014, 125 pts were enrolled: 66 in Ph1 (30-300 mg) and 59 in Ph2 (90 or 180 mg). Baseline characteristics: 58% female, median age 57 yr; diagnoses: NSCLC n = 117, other n = 8. 62 pts remain on study; median follow-up for all pts is 3.1 mo (max= 24.4 mo, ongoing). The most common treatment-emergent adverse events (≥20%) were nausea (40%), fatigue (34%), diarrhea (34%), cough (26%), headache (25%), and vomiting (21%), which were generally Grade 1/2 in severity. Early onset pulmonary symptoms (dyspnea with hypoxia and/or new findings on chest imaging) were observed in 12/125 (10%) pts: 6/44 (14%) at 180 mg qd and 1/38 (3%) at 90 mg qd. Symptoms occurred within 7 days following initiation of AP26113, required medical attention, and occurred at lower rates with lower doses. Pts continue to be enrolled at 90 mg qd. Among 51 evaluable ALK+ NSCLC pts with prior crizotinib, 35 (69%) responded. Duration of response was 1.6– 14.7+ mo. 23 had confirmed responses and 7 await confirmation. Among 55 evaluable pts with ALK+ NSCLC, median progression free survival is 10.9 mo. Independent radiological review conducted on 10 pts enrolled with untreated or progressing brain metastases showed 6/10 pts with regression in brain, including 4 with undetectable brain metastases following AP26113; 2 had stable disease, 2 progressed; 7/10 remain on study (range 2.7-19.5 mo). Updated data will be presented.

Conclusions

AP26113 has promising anti-tumor activity in pts with crizotinib-resistant ALK+ NSCLC, including pts with brain metastases. A randomized Ph2 trial evaluating either 90 mg qd or 90mg qd escalated to 180 mg qd in crizotinib-resistant ALK+ NSCLC has been initiated.

Disclosure

S. Gettinger: research funding (ARIAD); consultancy (ARIAD); honoraria (ARIAD); C. Langer: research funding (ARIAD); A. Shaw: consultancy (ARIAD); G.J. Weiss: consultancy (Genentech, Pfizer, Celgene, Quintiles, Medscape); N.I. Narasimhan: employment and equity ownership (ARIAD); D.J. Dorer: employment and equity ownership (ARIAD); V.M. Rivera: employment and equity ownership (ARIAD); T. Clackson: employment and equity ownership (ARIAD); F.G. Haluska: employment and equity ownership (ARIAD); R. Camidge: research funding (ARIAD); honoraria (ARIAD). All other authors have declared no conflicts of interest.