ALUNBRIG® (brigatinib) EFFICACY POST-CRIZOTINIB

ALTA Study Design

The efficacy of ALUNBRIG® (brigatinib) was evaluated in a global, two-arm, open-label, multicenter trial in adult patients with locally advanced or metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who had progressed on crizotinib.

222 Adult Patients

Locally advanced or metastatic ALK+ NSCLC
Progressed on crizotinib

Randomized 1:1

n=110

ALUNBRIG
90180-mg arm
180 mg once daily with a 7-day lead-in dose at 90 mg once daily

STRATIFIED BY:

CNS metastases at baseline (absent or present)

Best responses to prior crizotinib treatment

n=112

ALUNBRIG
90-mg once-daily arm

Median duration of follow-up of 8 months (RANGE: 0.1-20.2) For All Patients

Major efficacy outcome measure was confirmed overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST v1.1) as evaluated by an Independent Review Committee (IRC).

Additional efficacy outcome measures included investigator-assessed ORR, duration of response (DOR), intracranial ORR, and intracranial DOR.

 

Patient Demographics

Patient Characteristics at Entry Total Patients (N=222)
Median Age 54 years old
(range, 18-82; 23% aged ≥65)
Race
   White
   Asian
 
67%
31%
Sex
   Female
 
57%
ECOG performance status
   0
   1
 
36%
57%
Smoking history
   Never or former
 
95%
Cancer stage at study entry
   IV
 
98%
Tumor histology
   Adenocarcinoma
 
97%
Prior systemic chemotherapy 74%
Most common sites of metastases
   CNS
      Prior radiation to the brain
   Bone
   Liver
 
69%
61% (of those with brain metastasis)
39%
26%
Objective response to prior crizotinib 64%

ECOG, Eastern Cooperative Oncology Group.

Systemic Efficacy Outcomes

Results From the 8-Month Median Follow-upa

53%
overall
response rate
for the recommended dosing regimenb (90→180 mg)
as assessed by an IRC (95% CI: 43-62; 4.5% CR,
48% PR; n=110)
OVERALL RESPONSE RATE
IRC-Assessed Investigator-Assessed
90 mgc (n=112) 90→180 mgb (n=110) 90 mgc (n=112) 90→180 mgb (n=110)
48%
(95% CI: 39-58)
CR: 3.6% | PR: 45%
53%
(95% CI: 43-62)
CR: 4.5% | PR: 48%
45%
(95% CI: 35-54)
CR: 0.9% | PR: 44%
54%
(95% CI: 44-63)
CR: 3.6% | PR: 50%
MEDIAN DURATION OF RESPONSE (MONTHS)
13.8
(95% CI: 7.4-NE)
13.8
(95% CI: 9.3-NE)
13.8
(95% CI: 5.6-13.8)
11.1
(95% CI: 9.2-13.8)

Additional Results From the 2-Year Median Follow-upd

Study Limitations: ALTA was not a controlled trial and not prospectively designed for statistical comparisons between dosing arms.

16.7
months
median progression-free survival for the recommended dosing
regimenb (90→180 mg) as assessed by an IRC (95% CI: 11.6-21.4; n=110)1
MEDIAN PROGRESSION-FREE SURVIVAL (PFS)1,e
  IRC-Assessed Investigator-Assessed
90→180-mg Armb
@ 24-month median follow-upa (n=110)
16.7 months
(95% CI: 11.6-21.4)
15.6 months
(95% CI: 11.1-21.0)
90-mg Armc
@ 20-month median follow-upa (n=112)
9.2 months
(95% CI: 7.4-12.8)
9.2 months
(95% CI: 7.4-11.1)
MEDIAN OVERALL SURVIVAL (MONTHS)1,f
90→180-mg Armb
@ 24-month median follow-upa (n=110)
34.1 months
(95% CI: 27.7-NR)
90-mg Armc
@ 20-month median follow-upa (n=112)
29.5 months
(95% CI: 18.2-NR)

aThe median duration of follow-up was 8 months (range: 0.1-20.2).

bThe recommended dosing regimen is 90 mg orally once daily for the first 7 days. If tolerated during the first 7 days, increase dose to 180 mg orally once daily.

c90 mg once daily.

dAdditional outcomes calculated as of September 29, 2017, 2 years after last enrollment (median follow-up of 19.6 months [range: 0.1-35.2] in the 90-mg arm and 24.3 months [range: 0.1-39.2] in the 90→180-mg arm).1

eMedian PFS at the 8-month follow-up: 15.6 months (95% CI: 11.0-NR) by IRC assessment and 12.9 months (95% CI: 11.1-NR) by Investigator assessment for the 90→180-mg group; and 9.2 months (95% CI: 7.4-NR) by IRC assessment and 9.2 months (95% CI: 7.4-15.6) by Investigator assessment for the 90-mg group.1

fMedian OS had not been reached at the 8-month follow-up in either the 90→180-mg group or the 90-mg group.1

CI, confidence interval; CR, complete response; IRC, Independent Review Committee; NE, not estimable; NR, not reached; PFS, progression-free survival; PR, partial response.

Intracranial Efficacy Outcomes

Results From the 8-Month Median Follow-upa

67%
response rate
for the recommended dosing regimenb (90→180 mg) in patients
with measurablec brain metastases at baseline as assessed by an
IRC (95% CI: 41-87; 0 CR, 67% PR; n=12/18)
INTRACRANIAL ORR IN PATIENTS WITH MEASURABLEc BRAIN METASTASES AT BASELINE (IRC-ASSESSED)
90→180-mg Armb (n=18) 67% (12/18; 95% CI: 41-87; CR: 0, PR: 67%)
90-mg Armd (n=26) 42% (11/26; 95% CI: 23-63; CR: 7.7%, PR: 35%)
DURATION OF INTRACRANIAL RESPONSE
AMONG RESPONDERS WITH MEASURABLEc BRAIN METASTASES AT BASELINE (IRC-Assessed)
INTRACRANIAL DOR ≥6 MONTHS INTRACRANIAL DOR ≥12 MONTHS
64%
(7/11) in the
90-mg Armd
50%
(6/12) in the
90→180-mg Armb
36%
(4/11) in the
90-mg Armd
25%
(3/12) in the
90→180-mg Armb

Duration of intracranial response was measured from date of first intracranial response until intracranial disease progression (new lesions, intracranial target lesion diameter growth ≥20% from nadir, or unequivocal progression of nontarget lesions) or death.


Additional Results From the 2-Year Median Follow-upe

Study Limitations: ALTA was not a controlled trial and not prospectively designed for statistical comparisons between dosing arms.

18.4
months
progression-free survival for the recommended dosing
regimenb (90→180 mg) in patients with any brain metastases at
baseline as assessed by IRC (95% CI: 12.6-23.9; n=74)1
MEDIAN INTRACRANIAL PFS IN PATIENTS WITH ANY BRAIN METASTASES AT BASELINE1,f
  IRC-Assessed
90→180-mg Armb
@ 24-month median follow-up (n=74)
18.4 months
(95% CI: 12.6-23.9)
90-mg Armd
@ 20-month median follow-up (n=81)
12.8 months
(95% CI: 9.2-18.3)

aThe median duration of follow-up was 8 months (range: 0.1-20.2).

bThe recommended dosing regimen is 90 mg orally once daily for the first 7 days. If tolerated during the first 7 days, increase dose to 180 mg orally once daily.

c≥10 mm in longest diameter (at baseline).

d90 mg once daily.

eAdditional outcomes calculated as of September 29, 2017, 2 years after last enrollment (median follow-up of 19.6 months [range: 0.1-35.2] in the 90-mg arm and 24.3 months [range: 0.1-39.2] in the 90→180-mg arm).1

fMedian intracranial PFS at the 8-month follow-up: 12.8 months (95% CI: 11.0-NR; n=73) by IRC assessment for the 90→180-mg group and 15.6 months (95% CI: 7.3-15.7; n=80) by IRC assessment for the 90-mg group.1

CI, confidence interval; CR, complete response; IRC, Independent Review Committee; NE, not estimable; NR, not reached; PFS, progression-free survival; PR, partial response.


 
 

References

  1. Huber RM, Hansen KH, Paz-Ares Rodriguez L, et al. J Thorac Oncol. 2020;15(3):404-415.
  2. Kim DW, Tiseo M, Ahn MJ, et al. J Clin Oncol. 2017;35(22):2490-2498.

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In Vitro: ALUNBRIG Inhibited 17
ALK-Inhibitor-Resistant Mutations1,2

ALUNBRIG exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including the G1202R and L1196M mutants identified in NSCLC tumors in patients who had progressed on crizotinib.

 

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