Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19853

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    97P - Brigatinib in crizotinib-refractory ALK+ NSCLC: Updates from the pivotal randomized phase 2 Trial (ALTA) (ID 247)

    12:30 - 13:00  |  Author(s): H.J. Groen
    • 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

    rn	Arm A n = 112	Arm B n = 110	Total N = 222
    Confirmed ORR, n/N (%)	rn	rn	rn
    All pts[a]	50/112 (45)	59/110 (54)	109/222 (49)
    Race	rn	rn	rn
    Asian	18/39 (46)	18/30 (60)	36/69 (52)
    Non-Asian	32/73 (44)	41/80 (51)	73/153 (48)
    Prior chemotherapy	rn	rn	rn
    Yes	35/83 (42)	44/81 (54)	79/164 (48)
    No	15/29 (52)	15/29 (52)	30/58 (52)
    Best response to prior crizotinib	rn	rn	rn
    CR or PR	36/71 (51)	47/73 (64)	83/144 (58)
    Other	14/41 (34)	12/37 (32)	26/78 (33)
    Baseline brain metastases	rn	rn	rn
    Yes	31/80 (39)	43/74 (58)	74/154 (48)
    No	19/32 (59)	16/36 (44)	35/68 (51)
    Median PFS, months	rn	rn	rn
    All pts	9.2	12.9	11.1
    Race	rn	rn	rn
    Asian	8.8	11.1	11.1
    Non-Asian	9.2	12.9	11.8
    Prior chemotherapy	rn	rn	rn
    Yes	8.8	12.9	11.8
    No	9.2	8.1	9.2
    Best response to prior crizotinib	rn	rn	rn
    CR or PR	11.1	15.6	15.6
    Other	7.4	12.9	9.2
    Baseline brain metastases	rn	rn	rn
    Yes	9.2	11.8	11.1
    No	7.4	15.6	15.6

    rnCR = complete response, ORR = objective response rate, PFS = progression-free survival, PR = partial responsernaPrimary endpointrn
    
    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.