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Poster Display Session (ID 63)
- Event: ELCC 2017
- Type: Poster Display Session
- Presentations: 1
- Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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
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).
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.
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.
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
rnrnCR = complete response, ORR = objective response rate, PFS = progression-free survival, PR = partial responsernaPrimary endpointrn
rnrn rn Arm A n = 112rn Arm B n = 110rn Total N = 222rn rnrn Confirmed ORR, n/N (%)rn rn rn rn rnrn All pts[a]rn 50/112 (45)rn 59/110 (54)rn 109/222 (49)rn rnrn Racern rn rn rn rnrn Asianrn 18/39 (46)rn 18/30 (60)rn 36/69 (52)rn rnrn Non-Asianrn 32/73 (44)rn 41/80 (51)rn 73/153 (48)rn rnrn Prior chemotherapyrn rn rn rn rnrn Yesrn 35/83 (42)rn 44/81 (54)rn 79/164 (48)rn rnrn Norn 15/29 (52)rn 15/29 (52)rn 30/58 (52)rn rnrn Best response to prior crizotinibrn rn rn rn rnrn CR or PRrn 36/71 (51)rn 47/73 (64)rn 83/144 (58)rn rnrn Otherrn 14/41 (34)rn 12/37 (32)rn 26/78 (33)rn rnrn Baseline brain metastasesrn rn rn rn rnrn Yesrn 31/80 (39)rn 43/74 (58)rn 74/154 (48)rn rnrn Norn 19/32 (59)rn 16/36 (44)rn 35/68 (51)rn rnrn Median PFS, monthsrn rn rn rn rnrn All ptsrn 9.2rn 12.9rn 11.1rn rnrn Racern rn rn rn rnrn Asianrn 8.8rn 11.1rn 11.1rn rnrn Non-Asianrn 9.2rn 12.9rn 11.8rn rnrn Prior chemotherapyrn rn rn rn rnrn Yesrn 8.8rn 12.9rn 11.8rn rnrn Norn 9.2rn 8.1rn 9.2rn rnrn Best response to prior crizotinibrn rn rn rn rnrn CR or PRrn 11.1rn 15.6rn 15.6rn rnrn Otherrn 7.4rn 12.9rn 9.2rn rnrn Baseline brain metastasesrn rn rn rn rnrn Yesrn 9.2rn 11.8rn 11.1rn rnrnrn Norn 7.4rn 15.6rn 15.6rn
Clinical trial identification:
Legal entity responsible for the study:
ARIAD Pharmaceuticals, Inc.
ARIAD Pharmaceuticals, Inc.
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.