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Efficacy

ALK in Lung Cancer Trial of AP26113 (ALTA): evaluating the efficacy and safety of ALUNBRIG  (brigatinib)

ALTA: a phase 2, global, randomised, open-label, multicentre trial.

Objective: to access the efficacy and safety of two ALUNBRIG dosing regimens.

ALTA was not a controlled trial and not designed for statistical comparisons between dosing regimens.

Primary endpoint was confirmed ORR according to Response Evaluation Criteria In Solid Tumours (RECIST v1.1) as evaluated by investigator.

aPatients in the 90 mg arm were allowed to escalate to 180 mg after RECIST progression.



222
Adult Patients

Locally advanced or
metastatic ALK+ NSCLC

Progressed on crizotinib

Randomised 1:1

n=110

n=112

ALUNBRIG

180 mg regimen

180 mg once daily with a 7-day lead-in at 90 mg once daily

ALUNBRIG

90 mg once daily regimen

Stratified by:

Brain metastases at baseline (absent or present)
Best responses to prior crizotinib treatment

Disease progression requiring an alternate therapya

Intolerable toxicity

Other reasons for discontinuation

Planned follow-up:
2 years

More than half of patients on ALUNBRIG achieved a responsea with the 180 mg regimenb,3

Objective response rate (ORR) in the 180 mg regimenb: ITT population (n=110)3

Bar chart

Adapted from Huber MH, et al. 20183

a ORR per RECIST v1.1

b 180 mg once daily with 7-day lead-in at 90 mg once daily.

c Last scan date: 18 September 2017

Secondary endpoints3

Median DORc

  • Median DOR for the 180 mg regimenb (n=110): IRC-assessed, 15.7 months (95% CI 12.8–21.8); investigator-assessed, 13.8 (95% CI 10.2–19.3)

Median time to response1

  • 1.9 months in the 180 mg regimenb (n=110, investigator-assessed)

Two thirds of patients with measurablea brain metastases at baseline (n=18) achieved an intracranial responseb with ALUNBRIG1,3,4

Intracranial ORR per IRC in the 180 mg regimenc, in patients with measurable brain metastases at baseline (n=18)3

Bar chart

IRC-assessed median intracranial DOR in patients with measurablea brain metastases at baseline

Intracranial DOR in responders receiving the 180 mg regimen (n=12) was 16.6 months (95% CI 3.7–NR)c,3-6

In the subset of patients with measurable, active brain metastasesd (n=15), ORR was 73% (95% CI 45–92)4


Disease control rate

  • In patients with measurable brain metastases at baseline, intracranial disease control rate was 83% (95% CI 59-96) in the 180 mg regimenc (n=18)3

Adapted from Huber MH, et al. 20183

a ≥10 mm in longest diameter at baseline.

b Intracranial response was defined as a ≥30% decrease in measurable lesions or complete disappearance of lesions in patients with only non-measurable lesions.

c 180 mg once daily with 7-day lead-in at 90 mg once daily.

d Active brain metastases were defined as lesions without prior radiotherapy or with investigator-assessed progression after prior radiotherapy.

e Last scan date: 7 September 2017

Exceeds 1 year median PFS in ALK+ aNSCLC patients post crizotinib3

IRC-assessed systemic PFS with the 180 mg regimena: ITT population (n=110)

PFS line chart

Adapted from Huber MH, et al. 20183

a 180 mg once daily with 7-day lead-in at 90 mg once daily.

Median PFS by investigator assessment in the 180 mg regimena (n=110): 15.6 months (95% CI: 11.1-21.0).

Intracranial protection extending out to one and a half yearsa,3-6

IRC-assessed intracranial PFSb in patients with any brain metastases at baseline3

PFS line chart

Adapted from Huber MH, et al. 20183

aIn patients with brain metastases at baseline.

bIntracranial PFS does not include systemic (non-cranial) disease progression events.

c180 mg once daily with 7-day lead-in at 90 mg once daily.

Intracranial mDOR (IRC assessed) of 16.6 months (95% CI 3.7-NR) in patients with measurable brain metastases at baselines4-6

ALUNBRIG demonstrated median OS of more than 2.5 years3

OS with the 180 mg regimena: ITT population (n=110)

OS line chart

Adapted from Huber MH, et al. 20183

a 180 mg once daily with 7-day lead-in at 90 mg once daily.

One-year survival probability with the 180 mg regimen (n=110) was 80% (95% CI 71–87).