Table 2. Summary of clinical data – second-generation HSP90 inhibitors.

HSP90 inhibitor	Clinical stage	Combination	Disease	Response	Ref.
NVP-AUY922	Phase I	No	Advanced solid tumors	SD	[38]
	Phase II	No	NSCLC progressing on chemotherapy	Objective responses in patients with ALK rearrangement, EGFR/KRAS and ALK wild-type and mEGFR	[40]
	Phase II	Erlotinib	mEGFR NSCLC progressing on EGFR inhibitors	Objective responses in EGFRT790M and SD	[41]
	Phase Ib/II	Trastuzumab	HER2+ MBC refractory to trastuzumab	Objective responses	[42]
	Phase II	No	HER2+ or ER+ BC	Objective responses	[39]
	Phase I/II	Bortezomib	MM	Ongoing	NCT00708292
	Phase I/II	PI3K inhibitor	Advanced or metastatic gastric cancer	Ongoing	NCT01613950
	Phase I/II	ALK inhibitor	ALK-rearranged NSCLC	Ongoing	NCT01772797
	Phase I/II	Docetaxel	NSCLC with EGFR mutations	Ongoing	NCT01646125
	Phase I/II	Cetuximab	KRAS-mutated colorectal cancer	Ongoing	NCT01294826
AT-13387 Ganetespib	Phase I	No	Refractory solid tumors	Objective response in GIST and SD in follicular cell thyroid cancer, metastatic uveal melanoma and GIST	[45]
	Phase I/II	No	CRPC progressing on abiraterone	Ongoing	NCT01685268
		Abiraterone	CRPC progressing on abiraterone	Ongoing	NCT01685268
	Phase I/II	No	NSCLC	Ongoing	NCT01712217
		Crizotinib	NSCLC	Ongoing	NCT01712217
	Phase I/II	No	Unresectable and/or metastatic GIST progressing on TKI	Ongoing	NCT01294202
		Imatinib	Unresectable and/or metastatic GIST progressing on TKI	Ongoing	NCT01294202
	Phase I	No	Unselected solid tumors	SD and 1 PR in colorectal cancer, PR in metastatic melanoma and SD in NSCLC	[49,50]
	Phase I/II	No	Hematological malignancies	No formal responses	[51,52]
	Phase II	No	NSCLC genotypic characterization of tumors for the presence of EGFR or KRAS mutation or the absence of these mutations	Responses in crizotinib-naïve patients with the EML4-ALK rearrangement	[53]
	Phase II	No	NSCLC crizotinib-naïve patients with the EML4-ALK rearrangement	Ongoing	NCT01562015
	Phase II	Docetaxel	NSCLC progressing on chemotherapy; AML; RCC	Objective responses	[58]
	Phase III	Docetaxel	NSCLC progressing on chemotherapy	Ongoing	NCT01798485
	Phase II	No	Unselected MBC	Objective not met but activity noted in trastuzumab refractory HER2+ and TNBC	[54]
	Phase II	No	GIST progressing on TKI	SD	[55]
	Phase I	Paclitaxel and trastuzumab	HER2+ trastuzumab refractory MBC	Ongoing	NCT02060253
KW-2478	Phase I	No	Lymphomas and leukemias	Completed	NCT00457782
	Phase I/II	Bortezomib	Relapsed and refractory MM	Objective responses	[61]
BIIB021	Phase I	No	CLL and advanced solid tumors	SD	[11]
	Phase II	No	GIST progressing on TKI	Metabolic responses as noted on FDG-PET	[66]
	Phase I	Trastuzumab	HER2+ BC	Objective responses with metabolic responses on FDG-PET as well	[67]
PU-H71	Phase I	No	Advanced solid tumors and lymphoma	Ongoing	NCT01393509
MPC-3100	Phase I	No	Recurrent or refractory cancer	SD	[73]
CUDC-305	Phase I	No	Advanced solid tumors	SD and PR in 2 patients (mKRAS NSCLC and BC)	[76]
	Phase I/II	Chemotherapy	NSCLC progressing on chemotherapy	ongoing	NCT01714037
SNX-5422	Phase I	No	Advanced solid tumors	Terminated due to ocular toxicity	[78]
	Phase I/II	No	Several HER2+ tumor types (NSLC, esophagogastric, breast, urothelial)	Ongoing	NCT01848756
NVP-HSP990	Phase I	No	Advanced solid tumors	No responses (drug development halted)	[81,82]
XL888	Phase I	No	Advanced solid tumors	Terminated	[11]
	Phase I	Vemurafenib	Unresectable mBRAF melanoma	Ongoing	NCT01657591

ALK: Anaplastic lymphoma kinase; AML: Acute myeloid leukemia; BC: Breast cancer; CLL: Chronic lymphocytic leukemia; CRPC: Castrate-resistant prostate cancer; EML4-ALK: Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase; FDG: Fluorodeoxyglucose; GIST: Gastrointestinal stromal tumors; NSCLC: non-small cell lung cancer; MBC: Metastatic breast cancer; MM: Multiple myeloma; PET: Positron emission tomography; PI3K: Phosphatidylinositol 3-kinase; PR: Partial response; SD: Stable disease; TKI: Tyrosine kinase inhibitor; TNBC: Triple-negative breast cancer.