▶ Median PFS for LORBRENA^TM was not reached.

▶ The percentage of patients who were alive without disease progression at 12 months was 78% (95% confidence interval [CI], 70 to 84) in LORBRENA^TM group and 39% (95% CI,30 to 48) in the crizotinib group.

Primary endpoint

^†Based on 1-sided stratified log-rank test.
 

BICR: Blinded Independent Central Review; BID=twice daily; CNS: central nervous system; ECOG PS: Eastern Cooperative Oncology Group Performance Status; QD: once daily; RECIST v1.1: Response Evaluation Criteria in Solid Tumors version 1.1; HR: hazard ratio; PFS: progression-free survival.

Individual responses in the primary analysis of the LORBRENA™ Registrational Study²

Figure: Best percentage change in tumour size from baseline
(A) EXP1: treatment-naive patients. (B) EXP2–3A: previous crizotinib with or without 1–2 chemotherapy regimens. (C) EXP3B: previous non-crizotinib ALK TKI with or without chemotherapy. (D) EXP4–5: two or more previous ALK TKIs with or without chemotherapy.

*off treatment or PD occurred.

Abbreviations: ALK, Anaplastic lymphoma kinase; CNS, Central nervous system; CT, Chemotherapy; DoR, Duration of response; ICR, Independent central review; IQR, Interquartile range; NSCLC, Non-small cell lung cancer; ORR, Objective response rate; PD, Progressive disease; PFS, Progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; TKI, Tyrosine kinase inhibitor.

ORR, PFS and DoR results for patients treated with prior ALK TKIs²

Data cut-off: 2 February 2018.³
 

^†Objective tumor response (defined as complete response or partial response) according to RECIST version 1.1, as assessed by ICR.²
 

Abbreviations: ALK, Anaplastic lymphoma kinase; CNS, Central nervous system; CT, Chemotherapy; DoR, Duration of response; ICR, Independent central review; IQR, Interquartile range; NR, Not reached; NSCLC, Non-small cell lung cancer; ORR, Objective response rate; PD, Progressive disease; PFS, Progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; TKI, Tyrosine kinase inhibitor.a

Time to intracranial progression was defined as the time from randomization to the first objective progression of central nervous system disease (either new brain metastases or progression of existing brain metastases).

• Percentage of patients who were alive without CNS progression at 12 months²

-60% (95% CI: 49-69) with crizotinib
 

^‡ Time from randomization to the first objective progression of CNS disease (either new brain metastases or progression of existing brain metastases).²
 

Abbreviations: CNS: central nervous system; ORR: overall response rate; DoR: duration of response.

Data cut-off: 15 March 2017.²

* Objective tumour response (defined as complete response or partial response) according to RECIST version 1.1, as assessed by ICR.²
 

Abbreviations: ALK, Anaplastic lymphoma kinase; CNS, Central nervous system; CT, Chemotherapy; DoR, Duration of response; ICR, Independent central review; IQR, Interquartile range; NC, Not calculated; NSCLC, Non-small cell lung cancer; ORR, Objective response rate; PFS, Progression-free survival; TKI, Tyrosine kinase inhibitor.

In cohorts EXP3B, 4–5, the intracranial ORR was >50%.^2*

Data cut-off 15 March 2017.²

*In patients with at least one measurable brain metastasis at baseline.^2
†Patients predominantly received either alectinib or ceritinib as the last ALK TKI ± CT before LORBRENA.^2
‡Intracranial objective tumor response (defined as complete response or partial response) according to modified RECIST version 1.1 which allowed for up to five CNS target lesions, as assessed by ICR.²

Abbreviations: ALK, Anaplastic lymphoma kinase; CNS, Central nervous system; CI, Confidence interval; CR, Complete response; CT, Chemotherapy; DoR, Duration of response; IC, Intracranial; ICR, Independent central review; IQR, Interquartile range; NC, Not calculated; NR, Not reached; NSCLC, Non-small cell lung cancer; ORR, Objective response rate; PFS, Progression-free survival; PR, Partial response; RECIST, Response Evaluation Criteria in Solid Tumors; TKI, Tyrosine kinase inhibitor.

• Data show that ALK resistance mutations were present in 56% of patients progressing on second-generation ALK TKIs (n=48)^2*

Individual responses of patients who have failed ≥1 prior 2^nd-generation ALK TKI (EXP3B–5), according to ALK mutation status^3§

*Ceritinib, 54%; alectinib, 53%; and brigatinib, 71%. A retrospective analysis of 103 repeat biopsies taken from ALK+ patients following progression on a 1st- or 2nd-generation ALK inhibitor.^2
†In vitro data; absolute IC₅₀ values of crizotinib, ceritinib, alectinib, brigatinib and LORBENA™ on cellular ALK phosphorylation in Ba/F3 cells harboring wild-type EML4-ALK variant 1 or various EML4-ALK resistance mutations are depicted.^2
‡In Ba/F3 cells, ALKF1174C and ALKI1171T appear sensitive to ceritinib and alectinib, respectively; however, these mutations may not be susceptible to these agents in vivo based upon previous clinical reports.^2
§ALK mutation status determined by tissue genotyping.³
 

Abbreviations: ALK, Anaplastic lymphoma kinase; CI, confidence interval; CNS, Central nervous system; CR, Complete response; CT, Chemotherapy; DoR, Duration of response; IC50, Half maximal inhibitory concentration; NSCLC, Non-small cell lung cancer; ORR, Objective response rate; PFS, Progression-free survival; TKI, Tyrosine kinase inhibitor.