testes along with microscopic evidence of hypospermatogenesis; these effects were reversible during the recovery period.
14 CLINICAL STUDIES
The efficacy of ALUNBRIG was demonstrated in a two-arm, open-label, multicenter trial (ALTA, NCT02094573) in adult patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who had progressed on crizotinib. The study required patients to have a documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit test. Key eligibility criteria included an ECOG Performance Status of 0-2 and progression on crizotinib. Neurologically stable patients with central nervous system (CNS) metastases were permitted to enroll. Patients with a history of interstitial lung disease or drug-related pneumonitis or who had received crizotinib within 3 days of the first dose of brigatinib were excluded. The major efficacy outcome measure was confirmed overall response rate (ORR) according to Response eva luation Criteria in Solid Tumors (RECIST v1.1) as eva luated by an Independent Review Committee (IRC). Additional efficacy outcome measures included Investigator-assessed ORR, duration of response (DOR), intracranial ORR, and intracranial DOR.
A total of 222 patients were randomized to receive ALUNBRIG either 90 mg once daily (90 mg arm; n=112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (90→180 mg arm; n=110). Randomization was stratified by brain metastases (present versus absent) and best prior response to crizotinib (complete or partial response versus any other response/uneva luable).
Baseline demographic characteristics of the overall study population were: median age 54 years (range 18 to 82, 23% 65 and over), 67% White and 31% Asian, 57% female, 36% ECOG PS 0 and 57% ECOG PS 1, and 95% never or former smokers. The disease characteristics of the overall study population were: Stage IV disease in 98%, adenocarcinoma histology in 97%, prior systemic chemotherapy in 74%, metastatic disease to the brain in 69% (61% had received prior radiation to the brain), bone metastases in 39%, and liver metastases in 26% of patients. Sixty-four percent of patients had an objective response to prior crizotinib.
The median duration of follow-up was 8 months (range: 0.1-20.2). Efficacy results from ALTA are summarized in Table 5.
Table 5: ALTA Efficacy Results
Efficacy parameter IRC Assessment Investigator Assessment
90 mg once daily 90→180 mg once daily 90 mg once daily 90→180 mg once daily
(N=112) (N=110) (N=112) (N=110)
CI = Confidence Interval; NE = Not Estimable
Overall Response Rate (95% CI) 48% (39-58) 53% (43-62) 45% (35-54) 54% (44-63)
Complete Response, n (%) 4 (3.6%) 5 (4.5%) 1 (0.9%) 4 (3.6%)
Partial Response, n (%) 50 (45%) 53 (48%) 49 (44%) 55 (50%)
Duration of Response, median in months
(95% CI) 13.8
(7.4-NE) 13.8
(9.3-NE) 13.8
(5.6-13.8) 11.1
(9.2-13.8)
IRC assessment of intracranial ORR and intracranial DOR according to RECIST v1.1 in the subgroup of 44 patients with measurable brain metastases (≥10 mm in longest diameter) at baseline are summarized in Table 6. Duration of intracranial response was me |
