Table 3.
Clinical trials of glutaminase inhibitor CB-839 (Telaglenastat) against various types of cancers.
| Trial identifier (ClinicalTrials.gov) | Phase and Recruitment Status | Intervention/ treatment |
Disease | Outcome | Ref |
|---|---|---|---|---|---|
| NCT02071927 | Phase 1, completed | CB-839 or CB-839 + Azacytidine |
Acute myeloid leukemia and acute lymphocytic leukemia | CB-839 was well tolerated and robustly inhibited GLS in blood platelets and in tumors. | (226) |
| NCT02071888 | Phase 1, completed | CB-839 or CB-839 + Dexamethasone or CB-839 + Pomalidomide + Dexamethasone |
Non-Hodgkin’s lymphoma and multiple myeloma, etc | CB-839 was well tolerated and robustly inhibited GLS in blood platelets and in tumors. | (227) |
| NCT02071862 | Phase 1, completed | CB-839 or CB-839 + Paclitaxel/Everolimus/Erlotinib/Docetaxel/Cabozantinib | Solid tumors, triple-negative breast cancer, non-small cell lung cancer renal cell carcinoma mesothelioma, etc |
CB-839 showed an accep table safety profile, significant glutaminase inhibition, and preliminary signs of clinical activity in multiple tumor types. |
(228–231) |
| NCT02771626 | Phase 1/2, completed | CB-839 + Nivolumab | Melanoma, clear cell renal cell carcinoma and non-small cell lung cancer | The combination of CB-839 + nivolumab was well tolerated and disease control in MEL, ccRCC and NSCLC was encouraging. | (232) |
| NCT03057600 | Phase 2, completed | CB-839 + Paclitaxel | Triple-negative breast cancer | Pac + CB-839 had clinical activity and was well tolerated. | (233) |
| NCT03163667 | Phase 2, completed | CB-839 + Everolimus Placebo + Everolimus | Clear cell renal cell carcinoma | ENTRATA met its primary endpoint, supporting GLS inhibition with CB-839 as a new therapeutic approach in RCC. | (234) |
| NCT03263429 | Phase 1/2, recruiting | CB-839 + Panitumumab + Irinotecan Hydrochloride (phase I only) | Metastatic or refractory RAS wild type colorectal cancer | Phase 1: Triplet combination was tolerable at full doses of each drug, and preliminary antitumor activity was observed in a majority of patients. Phase 2 is in progress. |
(235) |
| NCT02861300 | Phase 1/2 active, not recruiting | CB-839 + Capecitabine | Solid tumor, colorectal cancer, colon cancer, rectal cancer | Patients with PIK3CA mutant CRC experienced prolonged progression-free survival. Phase 2 is pending. |
(236) |
| NCT03047993 | Phase 1/2 active, not recruiting | CB-839 + Azacitidine | (High risk) myelodysplastic Syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia | Combination treatment is a safe and effective regimen for patients with advanced MDS. Response in previously-treated and genomically high-risk patients was encouraging. The trial continues. | (237, 238) |
| NCT03428217 | Phase 2, completed | CB-839 + Cabozantinib Placebo + Cabozantinib |
Advanced or metastatic renal cell carcinoma | Combination treatment did not meet the primary end point of improved progression-free survival. | (239, 240) |
| NCT03965845 | Phase 1/2, completed | CB-839 + Palbociclib | Solid tumors, non-small cell lung cancer, colorectal cancer, KRAS mutation | N/A | N/A |
| NCT03528642 | Phase 1, active, not recruiting | CB-839 HCl + Temozolomide + Radiation | Astrocytoma, IDH-mutant, Grade 2 and 3 | In progress | N/A |
| NCT03798678 | Phase 1, active, not recruiting | CB-839 HCl + Carfilzomib + Dexamethasone | Recurrent or refractory plasma cell myeloma | Triplet combination was well tolerated. Ongoing correlative studies could provide mechanistic insight into which patients could benefit the most from Telaglenastat in combination with proteasome inhibitors. | (241) |
| NCT03831932 | Phase 1/2, recruiting | CB-839 HCl + Osimertinib | Advanced or metastatic lung non-small cell carcinoma and stage IV lung cancer AJCC v8 | In progress | N/A |
| NCT03872427 | Phase 2, active, not recruiting | CB-839 | Advanced malignant solid neoplasm, metastatic malignant solid neoplasm, and NF1 mutation positive malignant peripheral nerve sheath tumor, etc | In progress | N/A |
| NCT04250545 | Phase 1, recruiting | CB-839 HCl + Sapanisertib | Metastatic or recurrent lung non-small cell carcinoma, Stage IV/IVA/IVB Lung Cancer AJCC v8 | The dose finding portion of phase 1 showed the combination treatment is safe and tolerable at the recommended expansion dose. The trial continues. | (242) |
| NCT04265534 | Phase 2, terminated | CB-839 + Pembrolizumab + Carboplatin/pemetrexed | KEAP1/NRF2/NFE2L2 mutated (non-squamous) non-small cell lung cancer |
Lack of clinical benefit | N/A |
| NCT03944902 | Phase 1, terminated | CB-839 + Niraparib | (Resistant BRCA -wild-type) ovarian cancer | The actual enrollment was only one and the participant is now off study. | N/A |
| NCT03875313 | Phase 1/2, terminated | CB-839 + Talazoparib | Solid tumor, clear cell renal cell carcinoma, colorectal cancer, etc | The study was terminated due to slow enrollment. | N/A |
| NCT04824937 | Phase 2, not yet recruiting |
CB-839 + Talazoparib | Metastatic prostate cancer | N/A | N/A |
| NCT05521997 | Phase 2, not yet recruiting |
CB-839 + Radiation + Cisplatin | Advanced cervical carcinoma | N/A | N/A |
ccRCC, clear cell renal cell carcinoma; CRC, colorectal cancer; MEL, melanoma; MDS, myelodysplastic syndrome; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma.