Current Insights on the Treatment of Anaplastic Lymphoma Kinase-Positive Metastatic Non-Small Cell Lung Cancer: Focus on Brigatinib

Figures & data

Table 1 Clinical Trials with Brigatinib in Advanced ALK-Positive NSCLC

	Phase	Patients	Key Inclusion Criteria	Treatment	Primary Endpoint	Results
NCT01449461	I/II	137	No previous ALK-targeted TKIs, with the exception of crizotinib.	Phase I: brigatinib 30−300 mg Phase II: brigatinib 90 mg; or 180 mg or 180 mg with a 7-day lead-in at 90 mg	ORR (phase II)	Cohort 1: ORR: 100% Cohort 2: ORR: 74% Cohort 3: ORR: 0% Cohort 4: ORR: 17% Cohort 5: ORR: 83%
NCT02094573 ALTA	II	222	Locally advanced or metastatic ALK+ NSCLC. Progressive disease while on crizotinib.	Arm A: brigatinib 90 mg Arm B: brigatinib180 mg with a 7-day lead-in at 90 mg	ORR	Arm A: ORR: 46% Arm B: ORR: 56%
NCT02737501 ALTA-1L	III	275	Stage IIIB (locally advanced or recurrent and not a candidate for definitive multimodality therapy) or stage IV ALK+ NSCLC. No previous ALK-targeted TKIs. No more than one previous systemic treatment for advanced NSCLC	Brigatinib180 mg with a 7-day lead-in at 90 mg or crizotinib, 250 mg twice daily	BIRC-assessed PFS	3-year BIRC PFS: 43% (brigatinib) 19% (crizotinib)
NCT03410108 J-ALTA	II	104	Brigatinib180 mg with a 7-day lead-in at 90 mg	Stage IIIB/IIIC/IV ALK-positive NSCLC. No previous ALK-targeted TKIs.	ORR (main refractory expansion cohort)*	ORR: 34%

Notes: *Independent review committee (IRC)–assessed confirmed ORR.

Abbreviations: TKIs, tyrosine kinase inhibitors; NSCLC, non-small cell lung cancer; ORR, objective response rate; PFS, progression-free survival; BIRC, blinded independent central review.

Table 2 Ongoing Phase II–III Clinical Trials with Brigatinib in Advanced ALK-Positive NSCLC

Trial	Phase Trial	Estimated Enrollment	Main Inclusion Criteria	Arms	Primary Endpoint
NCT04318938 (ABP trial)	II	116 pts	No prior therapy for advanced ALK-positive NSCLC	Brigatinib vs second-generation ALK inhibitor	PFS*
NCT03596866 (ALTA-3)	III	246 pts	PD while on crizotinib no other ALK inhibitor other than crizotinib	Brigatinib vs alectinib	PFS
NCT02706626 (ATOMIC ARI-AT-002 trial)	II	120 pts	Previous treatment with a second-generation ALK inhibitor	Brigatinib	ORR
NCT04074993	II	35 pts	Previous treatment with one ALK inhibitor ALK-rearrangement, as detected via the blood somatic mutation assay	Brigatinib	ORR
NCT04223596 (CUBIK)	II	33 pts	No prior treatment for advanced NSCLC	Brigatinib	ORR
NCT04634110 (B3i trial)	II	19 pts	Previously untreated brain metastases	Brigatinib	DCR

Note: *Of first-line treatment.

Abbreviations: Pts, patients; PFS, progression-free survival; NSCLC, non-small cell lung cancer; ORR, objective response rate; DCR, disease control rate.