Table 4.

Phase I and II trials using other agents that modulate metabolism.

Agent	Mechanism	Phase/Trial/Number of patients	Outcome
Asparaginase	Depletes asparagine	2/Ovarian/4	Terminated early d/t toxicity (4)
ADI-PEG 20	Inhibits arginine deaminase	1 & 2/Advanced Melanoma/31 2/Advanced solid tumors (+docetaxel)/18 2/Advanced HCC/71	SD in 9 patients (4 with uveal melanoma) 1 PR, 6 SD 31% SD
EGCG	Induction of apoptosis	1b/Hormone-receptor negative breast cancer/40 2/Chronic lymphocytic leukemia/42 2/Advanced ovarian cancer/16	Well tolerated in chemopreventive setting 69% Rai stage 0 – 2 with biologic response Five women without recurrence at 18m
AG-221	IDH2 inhibitor	1: Hematologic malignancies with IDH2 mutations/22	6/7 evaluable pts with RR
cG250 (Rencarex®)	Chimeric monoclonal antibody against CAIX	1/Advanced renal cell carcinoma/23 1 & 2/Metastatic renal cell carcinoma (+IFN-a)/31	Well tolerated, 74% SD at 3m 2 PR, 14 SD at 4m
E7070 (Indisulam)	Decreases glutathione synthase and glutathione reductase	1/Advanced solid tumors (+Xeloda)/35 1/Advanced solid tumors (+carboplatin)/16 2/Metastatic renal cell carcinoma/30 2/Advanced NSCLC/44	2 PR, 17 SD Well tolerated Majority of patients with PD* 1 MR

ADI: Arginine deiminase; CAIX: Carbonic anhydrase IX; EGCG: Epigallocatechin gallate; HCC: Hepatocellular carcinoma; IDH: Isocitrate dehydrogenase; PR: Partial remission; SD: Stable disease.