Brigatinib (BRG) in patients (Pts) with anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) in a phase 1/2 trial

Background

BRG, an investigational oral ALK inhibitor with preclinical activity against ALK mutants resistant to crizotinib (CRZ) and other ALK inhibitors, was studied in pts with advanced malignancies, including ALK+ NSCLC.

Methods

137 pts (ALK+ NSCLC, n = 79) received oral BRG (30–300 mg/d) in an ongoing phase 1/2, single-arm, open-label, multicenter trial (NCT01449461). We report activity by RECIST v1.1 (in ALK+ NSCLC pts) and safety (in all pts).

Results

As of 16 Nov 2015, 36/79 (46%) ALK+ NSCLC pts (median age 54 years, 49% female, 90% with prior CRZ) continued to receive BRG. Median time on treatment was 17.0 months (1 day to 44.4 months). 51/71 (72%) pts with prior CRZ and 8/8 (100%) CRZ-naive pts achieved an objective response (see table). In pts with prior CRZ, median duration of response in confirmed responders and progression-free survival in all pts were 14.5 months and 12.9 months, respectively; in CRZ-naive pts, medians were not reached. Treatment-emergent adverse events (AEs) in ≥30% of all pts (mostly grade 1/2): nausea 51%; fatigue 42%; diarrhea 41%; headache 34%; cough 33%. Serious treatment-emergent AEs (excluding disease progression; any cause) in ≥2% of all pts: dyspnea 7%; pneumonia 7%; hypoxia 5%; pulmonary embolism 3%; malignant pericardial effusion 2%; pneumonitis 2%. Of 137 pts, 14 (10%) discontinued due to an AE.

Conclusions

BRG had substantial antitumor activity in ALK+ NSCLC pts and an acceptable safety profile in this study. A pivotal, randomized, phase 2 trial of BRG in CRZ-resistant ALK+ NSCLC (ALTA) evaluating 90 mg qd vs 180 mg qd with a 7-day lead-in at 90 mg is ongoing.

Response in ALK+ NSCLC Pts, With Prior CRZ Exposure (All and at Doses Explored in Phase 2) and CRZ-Naive

Data are n (%) CR = complete response, DCR = disease control rate, ORR = objective response rate, PR = partial response, SD = stable disease ^a 180 mg qd with 7-day lead-in at 90 mg ^b Includes 21 pts at 180 mg qd and 2 pts at 90 mg bid ^c All confirmed ^d Includes non-CR/non–progressive disease in pts with nonmeasurable disease at baseline

Clinical trial identification

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc.

Funding

ARIAD Pharmaceuticals, Inc.

Disclosure

L. Bazhenova: Stock and other ownership interests (Epic Sciences), honoraria (Novartis), consulting or advisory role (AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Genoptix, Heat Biologics, Pfizer, Roche/Genentech, Seattle Genetics, and Trovagene), speakers bureau (AstraZeneca, Novartis, Pfizer, Roche/Genentech), research funding (AbbVie, ARIAD, Astellas, Astex, AstraZeneca, Boehringer Ingelheim, Chugai, Clovis Oncology, Eisai, Eli Lilly, Heat Biologics, Johnson & Johnson, MedImmune, Merck, Mirati, NanoCarrier, Novartis, Pfizer, Roche/Genentech). S. Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech). K. Gold: Honoraria (BMS, Roche), consulting or advisory role (Pfizer), research funding (ARIAD, AstraZeneca, BMS, Puma, Roche/Genentech). C. Langer: Honoraria (BMS, Lilly/ImClone, Roche/Genentech), consulting or advisory role (Abbott, ARIAD, AstraZeneca, Bayer/Onyx, BMS, Cancer Support Community, Celgene, Clarient, Clovis Oncology, Lilly/ImClone, Merck, Millennium, Roche/Genentech), research funding (Advantagene, ARIAD, Celgene, Clovis Oncology, GSK, Inovio, Merck, Roche/Genentech). A. Shaw: Honoraria (Novartis, Pfizer, Roche), consulting or advisory role (ARIAD, Blueprint Medicines, Daiichi Sankyo, EMD Serono, Ignyta, Novartis, Pfizer, Roche/Genentech, Taiho), research funding (ARIAD, Ignyta, Novartis, Pfizer). G. Weiss: Employment (Cancer Treatment Centers of America), consulting or advisory role (Blend Therapeutics, Paradigm, Pharmatech), speakers bureau (Amgen, Celgene, Medscape, Merck, Novartis, Pfizer, Quintiles), travel, accommodations, expenses (Cambridge Healthtech Institute, Nantworks, Pharmatech). J. Haney, V. Rivera, F. Haluska, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria, research funding (ARIAD). All other authors have declared no conflicts of interest.