14 CLINICAL STUDIES
14.1 ALK-Positive Metastatic NSCLC Previously Treated with an ALK Kinase Inhibitor
The efficacy of LORBRENA was demonstrated in a subgroup of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) previously treated with one or more ALK kinase inhibitors who were enrolled in a non-randomized, dose-ranging and activity-estimating, multi-cohort, multicenter study (Study B7461001; NCT01970865). Patients included in this subgroup were required to have metastatic disease with at least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), ECOG performance status of 0 to 2, and documented ALK rearrangement in tumor tissue as determined by fluorescence in situ hybridization (FISH) assay or by Immunohistochemistry (IHC), and received LORBRENA 100 mg orally once daily. Patients with asymptomatic CNS metastases, including patients with stable or decreasing steroid use within 2 weeks prior to study entry, were eligible. Patients with severe, acute, or chronic psychiatric conditions including suicidal ideation or behavior were excluded. In addition, for patients with ALK-positive metastatic NSCLC, the extent and type of prior treatment was specified for each individual cohort (see Table 4). The major efficacy outcome measures were overall response rate (ORR) and intracranial ORR, according to RECIST v1.1, as assessed by Independent Central Review (ICR) committee. Data were pooled across all subgroups listed in Table 4. Additional efficacy outcome measures included duration of response (DOR), and intracranial DOR.
A total of 215 patients were enrolled across the subgroups in Table 4. The distribution of patients by type and extent of prior therapy is provided in Table 4. The demographic characteristics across all 215 patients were: 59% female, 51% White, 34% Asian, and the median age was 53 years (29 to 85 years) with 18% of patients ≥65 years. The ECOG performance status at baseline was 0 or 1 in 96% of patients. All patients had metastatic disease and 95% had adenocarcinoma. Brain metastases as identified by ICR were present in 69% of patients; of these, 60% had received prior radiation to the brain and 60% (n=89) had measurable disease per ICR.
|Extent of prior therapy||Number of patients|
|Abbreviations: ALK=anaplastic lymphoma kinase; NSCLC=non-small cell lung cancer.|
|Prior crizotinib and no prior chemotherapy*||29|
|Prior crizotinib and 1–2 lines of prior chemotherapy*||35|
|Prior ALK inhibitor (not crizotinib) with or without prior chemotherapy*||28|
|Two prior ALK inhibitors with or without prior chemotherapy*||75|
|Three prior ALK inhibitors with or without prior chemotherapy*||48|
Efficacy results for Study B7461001 are summarized in Tables 5 and 6.
|Abbreviations: CI=confidence interval; N=number of patients.|
|Overall response rate* (95% CI)†||48% (42, 55)|
|Duration of response|
|Median, months‡ (95% CI)||12.5 (8.4, 23.7)|
An assessment of intracranial ORR and the duration of response for CNS metastases in the subgroup of 89 patients in Study B7461001 with baseline measurable lesions in the CNS according to RECIST v1.1 are summarized in Table 6. Of these, 56 (63%) patients received prior brain radiation, including 42 patients (47%) who completed brain radiation treatment at least 6 months before starting treatment with LORBRENA.
|Abbreviations: CI=confidence interval; N=number of patients; NR=not reached.|
|Intracranial response rate* (95% CI)†||60% (49, 70)|
|Duration of response|
|Median, months‡ (95% CI)||19.5 (12.4, NR)|
In exploratory analyses conducted in subgroups defined by prior therapy, the response rates to LORBRENA were:
- ORR = 39% (95% CI: 30, 48) in 119 patients who received crizotinib and at least one other ALK inhibitor, with or without prior chemotherapy
- ORR = 31% (95% CI: 9, 61) in 13 patients who received alectinib as their only ALK inhibitor, with or without prior chemotherapy
- ORR = 46% (95% CI: 19, 75) in 13 patients who received ceritinib as their only ALK inhibitor, with or without prior chemotherapy