Abstract 1195P
Background
In 2 planned interim analyses of ALTA-1L (NCT02737501), BRG BIRC-assessed PFS was superior to CRZ. We report final ALTA-1L results.
Methods
Patients (pts) with ALK TKI–naive advanced ALK+ NSCLC were enrolled and stratified by baseline (BL) brain metastases (BM) and prior chemotherapy (CT). One prior CT for advanced NSCLC and asymptomatic BM was allowed. Pts were randomized 1:1 to BRG 180 mg qd (7-day lead-in at 90 mg) or CRZ 250 mg BID. Pts in the CRZ arm were offered BRG at progression. Primary endpoint: BIRC-assessed PFS (RECIST v1.1). Secondary endpoints included confirmed iORR, iPFS by BIRC, OS, safety, and QoL.
Results
275 pts randomized (BRG/CRZ, n=137/138); median age 58/60 y; prior CT 26%/27%; BL BM 29%/30%. As of 29 Jan 2021 (last patient contact), median follow-up was (BRG/CRZ): 40.4/15.2 mo, with 166 (73/93) PFS events. BIRC-assessed PFS HR was 0.48 (95% CI: 0.35–0.66, log-rank P<0.0001); BRG mPFS was 24.0 mo (95% CI: 18.4–43.2) vs CRZ 11.1 mo (95% CI: 9.1–13.0); 3-yr PFS rate was (BRG/CRZ) 43%/19%. Investigator-assessed PFS HR was 0.43 (95% CI: 0.31–0.58, mPFS 30.8 vs 9.2 mo). mDoR (BIRC) was 33/14 mo. Median OS was not reached in either group (events BRG/CRZ: 41/51; HR: 0.81 [95% CI: 0.53–1.22]; log rank P=0.3311); 3-yr OS was 71%/68%. In pts with BL BM, OS HR was 0.43 (95% CI: 0.21–0.89; Table); in pts with no BL BM, 1.16 (0.69–1.93). Most common grade ≥3 TEAEs: BRG: increased CPK (26%) and lipase (15%), hypertension (14%); CRZ: increased ALT (10%), lipase, (8%), AST (7%). Any grade ILD/pneumonitis (BRG/CRZ): 4.4%/2.2%; discontinuation due to AE: 13.2%/8.8%. Median time to worsening in pt-reported global health status/QoL was (BRG/CRZ) 26.7/8.3 mo; HR: 0.69 (95% CI: 0.49–0.98). Table: 1195P
| Efficacy per BIRC | BRG | CRZ | P |
| BL brain metastases | |||
| any, n | 40 a | 41a | |
| PFS events, n (%) | 24 (60) | 31 (76) | |
| HR | 0.25 (0.14–0.46b) | <0.0001c | |
| OS events, n (%) | 11 (28) | 22 (54) | |
| 3-yr OS, % | 74 (57–85b) | 55 (38–69b) | |
| HR | 0.43 (0.21–0.89b) | 0.0199c | |
| 47d | 49d | ||
| None, n | 97a | 97a | |
| PFS events, n (%) | 49 (51) | 62 (64) | |
| HR | 0.62 (0.43–0.91b) | 0.0131c | |
| 90d | 89d | ||
| iPFS events, n (%) | 25 (28) | 23 (26) | |
| HR | 0.70 (0.39–1.26b) | 0.2410c | |
| Measurable, n | 18 | 23 | |
| iORRe, % | 78 (52–94b) | 30 (13–53b) | 0.0036f |
| Confirmed iORR, % | 78 (52–94b) | 26 (10–48b) | 0.0014f |
| Median iDoRg, mo | 28 (6–NEb) | 9 (4–NEb) |
aPer investigator; b95% CI; cLog-rank; dPer BIRC; eResponse,≥1 assessment; fCochran-Mantel-Haenszel test; gConfirmed responders
Conclusions
BRG demonstrated durable overall and intracranial efficacy, and the tolerability profile remained consistent and manageable despite extended treatment duration, confirming BRG as an effective standard-of-care treatment in pts with treatment-naive ALK+ NSCLC.
Clinical trial identification
NCT02737501; Release date: 30 March 2016.
Editorial acknowledgement
Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc.
Legal entity responsible for the study
ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
S. Popat: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Lilly, Merck KGaA, Novartis, Roche, Takeda; Financial Interests, Institutional, Other, Sub-investigator: Amgen, MSD; Financial Interests, Institutional, Other, Coordinating PI: ARIAD, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Other, Local PI: AstraZeneca, GlaxoSmithKline, Roche, Trizel; Non-Financial Interests, Personal, Officer: European Society of Medical Oncology; Non-Financial Interests, Personal, Leadership Role: British Thoracic Oncology Group, European Thoracic Oncology Platform; Non-Financial Interests, Personal, Advisory Role: ALK Positive UK, International Association for the Study of Lung Cancer, Lung Cancer Europe, Ruth Strauss Foundation; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation. H.R. Kim: Financial Interests, Personal, Other, Honoraria, consulting or advisory role: AstraZeneca, Roche, Boehringer Ingelheim. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis; Financial Interests, Personal, Other, consulting or advisory role: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis. J.C. Yang: Financial Interests, Personal, Other, Honoraria or advisory role: Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals. J. Han: Financial Interests, Personal, Other, Research funding: Roche. M.J. Hochmair: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, consulting or advisory role: Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Takeda. K.H. Lee: Financial Interests, Personal, Other, Honoraria, advisory role: AstraZeneca, Eli Lilly, Boehringer Ingelheim. A. Delmonte: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, Boehringer Ingelheim. M.R. Garcia Campelo: Financial Interests, Personal, Invited Speaker, Consulting/advisory role: Takeda, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim, Pfizer, Janssen, Eli Lilly, MSD, Sanofi. D. Kim: Financial Interests, Institutional, Other, Research funding: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge B; Financial Interests, Personal, Other, travel/accommodations: Amgen, Daiichi Sankyo. F. Griesinger: Financial Interests, Personal, Other, Consulting or advisory role: ARIAD, Takeda, Roche, Novartis, Pfizer. E. Felip: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, MSD, Novartis, Pfizer, Roche, Takeda, Merck. R. Califano: Financial Interests, Personal, Other, Honoraria and consulting or advisory role: AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis. A. Spira: Financial Interests, Personal, Other, Consulting/advisory role: ARIAD, AstraZeneca, Clovis Oncology, Roche, Amgen, Mirati, BMS, Merck. S.N. Gettinger: Financial Interests, Personal, Invited Speaker, Consulting or advisory role: ARIAD, BMS, Janssen; Financial Interests, Personal, Other, Research funding: ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech. M. Tiseo: Financial Interests, Personal, Other, Speakers bureau or advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche. H.M. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. Y. Liu: Financial Interests, Personal, Full or part-time Employment: Takeda. F. Vranceanu: Financial Interests, Personal, Full or part-time Employment: Takeda. D.R. Camidge: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis; Financial Interests, Personal, Funding, Research funding: ARIAD/Takeda.