97P - Brigatinib in crizotinib-refractory ALK+ NSCLC: Updates from the pivotal randomized phase 2 Trial (ALTA)

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic malignancies
Non-small-cell lung cancer
Therapy
Presenter Maximilian Hochmair
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors M.J. Hochmair1, M. Tiseo2, K.L. Reckamp3, H.L. West4, H.J. Groen5, C.J. Langer6, W. Reichmann7, D. Kerstein7, D. Kim8, D.R. Camidge9
  • 1Otto Wagner Hospital, 1140 - Vienna/AT
  • 2Medical Oncology Unit, University Hospital of Parma, Parma/IT
  • 3City of Hope, Duarte/US
  • 4Swedish Cancer Institute, Seattle/US
  • 5University of Groningen and University Medical Center Groningen, Groningen/NL
  • 6University of Pennsylvania Abramson Cancer Center, Philadelphia/US
  • 7ARIAD Pharmaceuticals Inc., Cambridge/US
  • 8Seoul National University Hospital, Seoul/KR
  • 9University of Colorado Cancer Center Anschutz Cancer Pavilion, Aurora/US

Abstract

Background

In a phase 1/2 trial (NCT01449461), the investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib (BRG) showed promising activity in crizotinib-treated ALK-positive non–small cell lung cancer (ALK+ NSCLC) patients (pts); because tumor responses and adverse events (AEs) varied with starting dose, two BRG regimens were evaluated in ALTA (NCT02094573).

Methods

Pts with crizotinib-refractory advanced ALK+ NSCLC were stratified by presence of brain metastases and best response to prior crizotinib and randomized 1:1 to receive BRG at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. Investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 was the primary endpoint.

Results

222 pts were enrolled (112 in arm A, 110 in arm B); median age was 54 years, 57% were female, 74% had received chemotherapy, and 69% had brain metastases. As of 29 February 2016, 57%/69% of pts in arms A/B were receiving BRG, with 7.8/8.3-month median follow-up. Investigator-assessed efficacy by arm and subgroup is shown below. Per independent review committee, as of 16 May 2016, confirmed ORR was 48%/53% and median PFS was 9.2/15.6 months in arms A/B. Treatment-emergent AEs with ≥25% overall frequency (A/B, n = 109/n=110 treated) were nausea 33%/40%, diarrhea 19%/38%, headache 28%/27%, and cough 18%/34%; grade ≥3 events with ≥3% frequency were hypertension 6%/6%, increased blood creatine phosphokinase 3%/9%, pneumonia 3%/5%, and increased lipase 4%/3%. A subset of pulmonary AEs with early onset (median onset: Day 2) occurred in 14/219 (6%) treated pts (3%, grade ≥3); no such events occurred after escalation to 180 mg in arm B, and 7/14 pts were successfully retreated.

Conclusions

BRG yielded substantial efficacy, with an acceptable safety profile, in both arms. 180 mg with 90 mg lead-in showed an improvement in efficacy endpoints, particularly PFS, with no increase in early pulmonary AEs, compared with 90 mg. Investigator-Assessed Efficacy by Subgroup.rnTable: 97PDrn

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
rnArm A n = 112Arm B n = 110Total N = 222
Confirmed ORR, n/N (%)rnrnrn
 All ptsa50/112 (45)59/110 (54)109/222 (49)
 Racernrnrn
  Asian18/39 (46)18/30 (60)36/69 (52)
  Non-Asian32/73 (44)41/80 (51)73/153 (48)
 Prior chemotherapyrnrnrn
  Yes35/83 (42)44/81 (54)79/164 (48)
  No15/29 (52)15/29 (52)30/58 (52)
 Best response to prior crizotinibrnrnrn
  CR or PR36/71 (51)47/73 (64)83/144 (58)
  Other14/41 (34)12/37 (32)26/78 (33)
 Baseline brain metastasesrnrnrn
  Yes31/80 (39)43/74 (58)74/154 (48)
  No19/32 (59)16/36 (44)35/68 (51)
Median PFS, monthsrnrnrn
 All pts9.212.911.1
 Racernrnrn
  Asian8.811.111.1
  Non-Asian9.212.911.8
 Prior chemotherapyrnrnrn
  Yes8.812.911.8
  No9.28.19.2
 Best response to prior crizotinibrnrnrn
  CR or PR11.115.615.6
  Other7.412.99.2
 Baseline brain metastasesrnrnrn
  Yes9.211.811.1
  No7.415.615.6
rn

CR = complete response, ORR = objective response rate, PFS = progression-free survival, PR = partial response

rna

Primary endpoint

rn

Clinical trial identification

NCT02094573

Legal entity responsible for the study

ARIAD Pharmaceuticals, Inc.

Funding

ARIAD Pharmaceuticals, Inc.

Disclosure

M. Tiseo: Consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, Otsuka, Pierre Fabre), research funding (ARIAD). K.L. Reckamp: Consulting or advisory role (ARIAD), research funding (ARIAD). H.L. West: Consulting or advisory role (ARIAD, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Merck, Novartis, Pfizer, Roche/Genentech, Trovagene), speakers’ bureau (ARIAD, Eli Lilly, Roche/Genentech). H.J. Groen: Consulting or advisory role (Eli Lilly, MSD, Novartis, Pfizer, Roche). C.J. 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). W. Reichmann, D. Kerstein: Employment, stock and other ownership interests (ARIAD). D.R. Camidge: Honoraria (ARIAD), research funding (ARIAD). All other authors have declared no conflicts of interest.