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– ALTA-1L Met its Primary Endpoint Showing Superiority in Blinded Independent Review Committee-Assessed Progression-Free Survival Compared to Crizotinib –

– Data Will Be Presented During the Presidential Symposium at the 19th World Conference on Lung Cancer (WCLC) with Simultaneous Publication in The New England Journal of Medicine –
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CAMBRIDGE, Mass. & OSAKA, Japan-Saturday 29 September 2018 [ AETOS Wire ]

Takeda Pharmaceutical Company Limited (TSE: 4502) today announced results from the Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial, demonstrating that ALUNBRIG reduced the risk of disease progression or death, known as progression-free survival (PFS), as assessed by a blinded independent review committee (BIRC), by more than fifty percent compared to crizotinib in adults with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor. Findings from the first interim analysis of the ALTA-1L trial will be presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in Toronto on Tuesday, September 25, 2018. The data were also simultaneously published online in The New England Journal of Medicine. ALUNBRIG is currently not approved as first-line therapy for advanced ALK+ NSCLC.

ALTA-1L is a global, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor but may have received up to one prior regimen of chemotherapy in the advanced setting. Patients were eligible for study entry on the basis of locally determined ALK testing. Patients received either ALUNBRIG, 180 mg once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg twice daily. Treatment with ALUNBRIG resulted in superior PFS compared to crizotinib as assessed by a blinded independent review committee (hazard ratio = 0.49 [95 percent confidence interval (CI), 0.33 to 0.74]; log-rank p=0.0007), corresponding to a 51 percent reduction in the risk of disease progression or death. The safety profile associated with ALUNBRIG was generally consistent with the existing U.S. prescribing information.

“The ALK+ NSCLC treatment landscape has experienced tremendous change over the last decade, and the ALTA-1L trial demonstrates that brigatinib has the potential to be a key player in the first-line setting,” said D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and the lead investigator of ALTA-1L. “The ALTA-1L trial offers unique aspects, including the real-world applicability of the data. The study’s design offered enrollment to a broader population by allowing patients to participate even if they had received prior chemotherapy and enrolled patients based on local standard of care ALK testing as opposed to mandating confirmation at a central lab. We look forward to further follow-up, which will provide even better understanding of the role of brigatinib in the evolving landscape.”

“We are thrilled to share these highly anticipated results with the lung cancer community,” said David Kerstein MD, Global Clinical Lead for Brigatinib and Lung Cancer Clinical Portfolio Strategy Lead, Takeda. “The ALTA-1L data demonstrate that ALUNBRIG is superior to crizotinib in the first-line setting, reducing disease progression or death by more than half, with particularly pronounced activity in the brain. We would like to thank all the investigators, and especially the patients and their caregivers who participated in this important clinical research.”

Brigatinib vs Crizotinib in Patients with ALK Inhibitor-Naïve Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (Presidential Symposium on Tuesday, September 25, 8:30 a.m. ET at the Metro Toronto Convention Centre North Building, Plenary Hall)

Key findings, which will be presented by D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and lead investigator of ALTA-1L, include:

A total of 275 patients were randomized to either brigatinib (n=137) or crizotinib (n=138). The median age was 59 years (brigatinib, 58; crizotinib, 60) and 55% of patients in the trial were female (brigatinib, 50%; crizotinib 59%). Twenty-nine percent had brain metastases at baseline (brigatinib, 29%; crizotinib, 30%), with comparable pre-enrollment CNS radiotherapy rates. Overall, 27% of patients had prior chemotherapy in the locally advanced or metastatic setting (brigatinib, 26%; crizotinib, 27%).
At the data cutoff for the first interim analysis (February 19, 2018), at a median follow-up period of 11.0 and 9.3 months in the brigatinib arm and crizotinib arm, respectively, 95 patients (69%) in the brigatinib arm and 59 patients (43%) in the crizotinib arm remained on study treatment.
The trial has met the pre-specified threshold for superiority in the primary endpoint at the first interim analysis. With a total of 99 events, BIRC-assessed PFS with brigatinib was superior to crizotinib (hazard ratio, 0.49 [95% confidence interval (CI), 0.33 to 0.74]; log-rank p=0.0007).
Additional efficacy outcomes are presented in the table below:

ALTA-1L Efficacy Results

Efficacy Endpoint

Brigatinib

Crizotinib

Intention-to-treat population

n=137

n=138

BIRC-assessed PFS

Median, months (95% CI)

NR (NR to NR)

9.8 (9.0 to 12.9)

12-month estimate (95% CI)

67% (56% to 75%)

43% (32% to 53%)

Hazard ratio (95% CI)

0.49 (0.33 to 0.74)

Log-rank p-value

0.0007

Investigator-assessed PFS

Median, months (95% CI)

NR (NR to NR)

9.2 (7.4 to 12.9)

12-month estimate (95% CI)

69% (59% to 76%)

40% (30% to 50%)

Hazard ratio (95% CI)

0.45 (0.30 to 0.68)

Log-rank p-value

0.0001

BIRC-assessed confirmed ORR (95% CI)

71% (62% to 78%)

60% (51% to 68%)

P-value

0.07

BIRC-assessed overall ORR (objective response at 1 or more assessments) (95% CI)

76% (68% to 83%)

73% (65% to 80%)

Patients with BIRC-assessed brain metastases at baseline

n=43

n=47

Intracranial PFS

Median, months (95% CI)

NR (11.0 to NR)

5.6 (4.1 to 9.2)

12-month estimate (95% CI)

67% (47% to 80%)

21% (6% to 42%)

Hazard ratio (95% CI)

0.27 (0.13 to 0.54)

Log-rank p-value

<0.0001

Patients with BIRC-assessed measurable brain metastases at baseline

n=18

n=21

Confirmed intracranial ORR (95% CI)

78% (52% to 94%)

29% (11% to 52%)

P-value

0.0028

Overall intracranial ORR (objective response at 1 or more assessments) (95% CI)

83% (59% to 96%)

33% (15% to 57%)

NR = Not reached

CI = Confidence Interval

PFS= Progression-Free Survival

ORR= Objective Response Rate

The safety profile associated with ALUNBRIG was generally consistent with the existing U.S. prescribing information.
Any grade treatment-emergent adverse events that occurred at a higher incidence with brigatinib than with crizotinib by more than five percentage points were increased blood creatine phosphokinase (brigatinib, 39% vs crizotinib, 15%), cough (25% vs 16%), hypertension (23% vs 7%), and increased lipase (19% vs 12%).
Any grade treatment-emergent adverse events that occurred at a higher incidence with crizotinib than with brigatinib by more than five percentage points were nausea (crizotinib, 56% vs brigatinib, 26%), diarrhea (55% vs 49%), constipation (42% vs 15%), peripheral edema (39% vs 4%), vomiting (39% vs 18%), increased alanine aminotransferase (32% vs 19%), decreased appetite (20% vs 7%), photopsia (20% vs 1%), dysgeusia (19% vs 4%), and visual impairment (16% vs 0).
Grade 3 to 5 treatment-emergent adverse events occurred in 61% of the patients in the brigatinib arm and 55% of the patients in the crizotinib arm. Most common grade 3 or greater treatment-emergent adverse events for brigatinib were increased blood creatine phosphokinase (16%), increased lipase (13%), hypertension (10%), and increased amylase (5%); and for crizotinib were increased alanine aminotransferase (9%), increased aspartate aminotransferase (6%), and increased lipase (5%).
Interstitial lung disease/pneumonitis at any time occurred in 4% (5/136) of patients in the brigatinib arm and 2% (3/137) in the crizotinib arm. Interstitial lung disease/pneumonitis with early onset (defined as within 14 days of treatment initiation) was observed in 3% of patients in the brigatinib arm (onset: Days 3 to 8) and was not observed in the crizotinib arm.

View source version on businesswire.com: https://www.businesswire.com/news/home/20180925005644/en/

Contacts

Takeda Pharmaceutical Company Limited
Japanese Media
Kazumi Kobayashi, +81 3 3 278 2095
kazumi.kobayashi@takeda.com
or
European Media
Kate Burd, +41 79 514 9533
kate.burd@takeda.com
or
Media outside Japan/EU
Amanda Loder, +1-212-259-0491
Amanda.Loder@takeda.com

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