Table 1.

Clinical trials of glutaminase inhibitor CB-839 (Telaglenastat) as cancer therapeutics^a

Trial identifier	Study	Statusb	Outcome	Refs
NCT02071862 i	CB-839 monotherapy or in combination with paclitaxel, everolimus, erlotinib, docetaxel, or cabozantinib in solid tumors	Phase I, 210, completed	CB-839 was well-tolerated, had clinical efficacyc with cabozantinib (ORR = 50%, DCR = 100%) or with everolimus (DCR = 92%, PFS = 7.1 months) in metastatic RCC.	[80–83]
NCT02071888 ii	CB-839 monotherapy, in combination with low dose dexamethasone or pomalidomide and low dose dexamethasone in hematological tumors	Phase I, 25, completed	CB-839 monotherapy was well-tolerated in patients with multiple myeloma and lymphoma.	[84]
NCT02071927 iii	CB-839 monotherapy or in combination with azacitidine in leukemia	Phase I, 43, completed	Platelets and PBMCs showed GLS inhibition.	[85]
NCT02771626 iv	CB-839 in combination with PD-1 blocking antibody, nivolumab, in patients with melanoma, ccRCC, and NSCLC	Phase I/II, 118, completed	CB-839 with nivolumab was well-tolerated in melanoma (ORR = 19%) and RCC (ORR = 21%, DCR = 74%).	[86]
NCT02861300 v	CB-839 with capecitabine in solid tumors and fluoropyrimidine-resistant PIK3CA mutant colorectal cancer	Phase I/II, 53, recruiting	The median PFS was 16.5 weeks for all patients and 29.5 weeks for PIK3CA mutant CRC patients.	[87]
NCT02944435 vi	A pharmacokinetic study of CB-839 capsule and tablet formulations in healthy adults	Phase I, 14, completed	N/A	N/A
NCT03047993 vii	CB-839 in combination with azacitidine in patients with advanced MDS	Phase I/II, 40, recruiting	CB-839 with azacitidine was well-tolerated in MDS patients (ORR = 63%).	[88]
NCT03057600 viii	CB-839 in combination with paclitaxel in patients of African ancestry and non-African ancestry with advanced TNBC	Phase II, 52, completed	CB-839 with paclitaxel was well-tolerated in advanced TNBC patients (ORR = 43%, DCR = 79%).	[89]
NCT03163667ix ENTRATA	Everolimus in combination with placebo or CB-839 in patients with RCC	Phase II, 63, completed	ENTRATA met the primary end point: improved PFS when everolimus was used in combination with CB-839 vs. placebo (3.8 months vs. 1.9 months).	[90]
NCT03263429 x	Novel PET/CT imaging biomarkers of CB-839 in combination with panitumumab and irinotecan in patients with metastatic and refractory RAS wildtype colorectal cancer	Phase I/II, 40, recruiting	This trial showed tolerable triple combination at full dose of each drug.	[91]
NCT03428217xi CANTATA	Cabozantinib in combination with placebo or CB-839 in patients with metastatic RCC	Phase II, 445, active, not recruiting	The combination of CB-839 and cabozantinib did not improve PFS, the primary end point.	[92]xxii
NCT03528642 xii	CB-839 with radiation therapy and temozolomide in patients with IDH-mutated diffuse astrocytoma or anaplastic astrocytoma	Phase I, 40, recruiting	Ongoing trial.	[93]
NCT03798678 xiii	CB-839 in combination with carfilzomib and dexamethasone in patients with recurrent or refractory multiple myeloma	Phase I, 36, recruiting	Ongoing trial.	[94]
NCT03831932 xiv	CB-839 and osimertinib in patients with EGFR-mutated stage IV NSCLC	Phase I/II, 53, recruiting	Ongoing trial.	N/A
NCT03872427 xv	Basket Trial of CB-839 in patients with NF1 aberrations, NF1 mutant malignant peripheral nerve sheath tumors, KEAP1/NRF2 and LKB1 aberrant tumors	Phase II, 108, recruiting	Ongoing trial.	N/A
NCT03875313 xvi	CB-839 in combination with the PARP inhibitor talazoparib in patients with solid tumors	Phase I/II, 33, terminated	Slow enrollment.	N/A
NCT03944902 xvii	CB-839 in combination with niraparib in platinum-resistant BRCA-wildtype ovarian cancer patients	Phase I, 33, not yet recruiting	N/A	N/A
NCT03965845 xviii	CB-839 in combination with the CDK4/6 inhibitor palbociclib in patients with solid tumors	Phase I/II, 85, recruiting	Ongoing trial.	N/A
NCT04250545 xix	CB-839 in combination with MLN0128 (sapanisertib) in advanced stage NSCLC	Phase I, 85, recruiting	Ongoing trial.	N/A
NCT04265534xx KEAPSAKE	CB-839 with standard-of-care chemoimmunotherapy (pembrolizumab, carboplatin, and pemetrexed) in KEAP1/NRF2-mutated, nonsquamous NSCLC	Phase II, 120, recruiting	Ongoing trial.	N/A
NCT04540965 xxi	Impact of the histamine H2 receptor antagonist famotidine on the pharmacokinetics of CB-839 in healthy adults	Phase I, 22, recruiting	Ongoing trial.	N/A

^aAbbreviations: BRCA, breast cancer gene; ccRCC, clear cell renal cell carcinoma; CRC, colorectal cancers; DCR, disease control rate; EGFR, epidermal growth factor receptor; IDH, isocitrate dehydrogenase; MDS, myelodysplastic syndrome; NF1, neurofibromatosis type 1; NSCLC, non-small cell lung cancer; ORR, overall response rate; PARP, poly (ADP-ribose) polymerase; PBMC, peripheral blood mononuclear cell; PD-1, programmed death receptor-1; PET/CT, positron emission tomography computed tomography; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; RAS, rat sarcoma gene; RCC, renal cell carcinoma; TNBC, triple negative breast cancer.

^bPhase stages, enrollment numbers, current status.

^cCalithera Biosciences initiated phase 2 ENTRATA (NCT03163667) and CANTATA (NCT03428217) trials based on the encouraging clinical efficacy and safety data.