Table 1.

Comparative description of study designs.

Study Identifier Name Sponsor	Study Design	Setting	Biomarker/Population Selection	Treatment Arms	Primary Endpoint	Tissue Requirement for Biomarker Analysis
3.1. Trials with EGFR Pathway Targeted Therapies
NCT00637910 TAILOR Fatebenefratelli and Ophthalmic Hospital	Phase III Randomized Open label	2nd line	EGFR WT	Erlotinib Docetaxel	OS	Archived tissue
NCT01360554 ARCHER 1009 Pfizer	Phase III Randomized Double blind Superiority	2nd line 3rd line	none	Erlotinib Dacomitinib	PFS	Archived tissue
NCT01466660 LUX-Lung 7 Boehringer Ingelheim	Phase II Randomized Open label Superiority	1st line	EGFR mut Adenocarcinoma	Gefitinib Afatinib	PFS	No
NCT01523587 LUX-Lung 8 Boehringer Ingelheim	Phase III Randomized Open label Superiority	2nd line	Squamous cell carcinoma	Erlotinib Afatinib	PFS	Archived tissue
NCT01487265 SCRI Development Innovations, LLC/Novartis	Phase II Single arm	2nd line 3rd line 4th line	EGFR TKI sensitive	Erlotinib plus BKM120	PFS at 3 months	Archived tissue
NCT01294306 NCI	Phase II Single arm	Any line	Erlotinib sensitive	Erlotinib plus MK2206	EGFR mut: ORR	Archived tissue
					EGFR WT: DCR
NCT01229150 NCI	Phase II Randomized Open label	2nd line 3rd line	KRAS mut	KRAS mut: Selumetinib Selumetinib plus erlotinib	KRAS mut: ORR	Archived tissue
			KRAS WT	KRAS WT: Erlotinib Erlotinib plus selumetinib	KRAS WT: PFS
3.2. Trials with ALK Pathway Targeted Therapies
NCT01801111 Hoffmann-La Roche	Phase II Single arm	2nd line or higher	ALK translocation Prior progression on crizotinib	Erlotinib plus alectinib	ORR	No
NCT01449461 Ariad Pharmaceuticals	Phase II Single arm	Any line	ALK translocation Prior progression on crizotinib	AP26113	ORR	Archived tissue
			ALK translocation Crizotinib naive
3.3. Trials with MET and EGFR Pathway Combination Targeted Therapies
NCT01456325 MetLung Hoffmann-La Roche	Phase III Randomized Double blind	2nd line 3rd line	MET positive	Erlotinib Erlotinib plus onartuzumab	OS	Archived tissue
3.4. Trials with Angiogenesis and EGFR Pathway Combination Targeted Therapies
NCT01562028 BELIEF European Thoracic Oncology Platform/Spanish Lung Cancer Group	Phase II Single arm	1st line	EGFR mut Non Squamous	Erlotinib plus bevacizumab	PFS	Archived tissue
NCT01532089 Academic and Community Cancer Research United	Phase II Randomized Open label	1st line	EGFR mut Non Squamous	Erlotinib Erlotinib plus bevacizumab	PFS	No
3.5. Trials with Targeted Therapies from Multiple Pathways
NCT01306045 NCI	Phase II Non randomized Open label	EGFR mut: 1st line or higher	EGFR mut	EGFR mut: erlotinib KRAS, NRAS, HRAS, or BRAF mut: selumetinib	ORR	Archived tissue
		Other groups: 2nd line or higher	KRAS, NRAS, HRAS, or BRAF mut
			PI3K Activation	PI3K activation: MK2206
			HER2 activation	HER2 activation: lapatinib
			PDGFR mut or amplification or KIT mut	PDGFR mut or amplification or KIT mut: sunitinib
NCT01248247 BATTLE II M.D. Anderson Cancer Center	Phase II Randomized Open label	Any line	Adaptive randomization based on ongoing analysis that attests which treatment is best in the setting of specific biomarker patterns	Erlotinib Erlotinib plus MK2206 MK2206 plus selumetinib sorafenib	8 week PFS	Real time biopsy
3.6. Trials with Therapies Inhibiting Miscellaneous Targets
NCT00787267 TOP0801 DUKE University	Phase II Single arm	2nd line or higher	None	dasatinib	Biomarker predictors of response	Real time biopsy
NCT01514864 Bristol-Myers Squibb	Phase II Single arm	Any line	BRAF or DDR2 mutations	dasatinib	ORR	No
NCT01124864 Novartis Pharmaceuticals	Phase II Single arm	3rd or higher	EGFR mut	AUY922	Response at 18 weeks	Archived tissue Real time biopsy only for the modified EGFR mut group
			KRAS mut
			EGFR and KRAS WT
			ALK translocation
			Modified EGFR mut (EGFR mut with prior response to EGFR TKI)
NCT01788332 Lisette Nixon	Phase II Randomized Double blind	Maintenance after 1st line chemotherapy	Only patients with response to first line chemotherapy will be randomized	Olaparib Placebo	PFS	Archived tissue
NCT01560104 AbbVie	Phase II Randomized 2:1 Double blind	1st line	EGFR wild type	Carboplatin plus paclitaxel plus veliparib Carboplatin plus paclitaxel plus placebo	PFS	Archived tissue

Abbreviations: TKI, tyrosine kinase inhibitor; PFS, progression-free survival; OS, overall survival; mut, mutant; WT, wild-type; ORR odds ratio.