telaglenastat (CB-839) / Cornerstone Pharma, Synhale Therapeutics - LARVOL DELTA

BEGIN: A Basket Trial of Glutaminase inhibition with Telaglenastat in NF1, KEAP1/NRF2, and STK11/LKB1-Altered Tumors (AACR-NCI-EORTC 2025) - P2 | "While the clinical development of the agent was discontinued, these findings demonstrate preliminary clinical activity of GLS inhibition in NF1-mutant melanoma and MPNST, providing proof-of-concept and supporting further investigation with biomarker-driven combination strategies."

IO biomarker • Late-breaking abstract • Pan tumor • Brain Cancer • Melanoma • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • KEAP1 • NF1 • NFE2L2 • STK11

Cytosolic transport of citrate protects nutrient-austere pancreatic cancer from ferroptosis (AACR 2026) - "As observed with cultured cells under nutrient limitation, SLC25A1 function was revealed to be indispensable in pancreatic tumor microenvironment, and the reduced growth, due to the lack of SLC25A1 activity, was rescued with antioxidant NAC in preclinical models of PDAC. Lastly, SLC25A1 suppression was accompanied by elevated glutamine metabolism, and combination therapy with pharmacologic inhibitors of SLC25A1 and glutaminase inhibitor CB-839 dramatically suppressed tumor growth, highlighting this combinatorial approach as a potential therapeutic strategy in PDAC."

Oncology • Pancreatic Cancer • Solid Tumor • ACO1 • GPX4

Adaptive resistance mechanisms to mTOR inhibitor in lung squamous cell carcinoma (AACR 2026) - "Moreover, prolonged treatment of LUSC PDXs with TAK228 and the glutaminase inhibitor CB-839 led to upregulation of vascularization, which coincided with a rebound in tumor growth despite continued therapeutic administration. These findings highlight adaptive resistance mechanisms to small molecule inhibitors that target key metabolic pathways, lending insight into potential future clinical strategies for the treatment of LUSC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A ketogenic diet sensitizes pancreatic cancer to metabolic therapies (AACR 2026) - "We demonstrate that combining glutamine metabolism inhibitors, such as CB839 or 6-diazo-5-oxo-L-norleucine (DON), with a KD leads to robust anti-tumor effects in preclinical models of pancreatic cancer. Together, these findings demonstrate that a ketogenic diet exposes a metabolic and redox vulnerability in PDAC by increasing reliance on glutamine-driven anaplerosis and elevating intratumoral ROS. Exploiting this state with targeted metabolic inhibitors—alone or in combination with ROS-inducing agents—produces potent anti-tumor responses and highlights a promising therapeutic strategy for pancreatic cancer."

Oncology • Pancreatic Cancer • Solid Tumor

Network meta-analysis of second- and later-line therapies in advanced renal cell carcinoma: A comparative effectiveness approach. (ASCO-GU 2026) - "Lenvatinib + everolimus (HR 0.49 vs placebo) and atezolizumab + cabozantinib (HR 0.56 vs placebo) demonstrated the greatest OS benefit. Compared with other active regimens, lenvatinib + everolimus significantly improved OS versus everolimus and temsirolimus monotherapy, ranking highest for OS (P-score = 0.88)...Lenvatinib + everolimus also ranked first for ORR (P-score = 0.94), followed by belzutifan (P-score = 0.86)... In this NMA, lenvatinib + everolimus demonstrated the greatest overall efficacy across OS, PFS, and ORR, outperforming all other therapies except telaglenastat + cabozantinib in PFS. These findings suggest lenvatinib + everolimus as the leading option for second- or later-line therapy in advanced RCC. However, results should be interpreted with caution and warrant confirmation in future large, head-to-head randomized trials."

HEOR • Metastases • Retrospective data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A GCLC Inhibitor Enhances the Antitumor Efficacy of Glutathione Metabolic Pathway Inhibition in SMARCB1-Deficient Rhabdoid Tumors. (PubMed, Cancer Res) - "Significant synergistic effects were observed when GCLC inhibitors were combined with agents targeting the GSH synthesis pathway, specifically SLC7A11 inhibitors and the glutaminase inhibitor telaglenastat...These findings highlight the vulnerability of glutathione metabolism in SMARCB1-deficient cancers, suggesting that a GCLC inhibitor may be a promising therapeutic option. This study provides a preclinical foundation for the development of effective treatment strategies for SMARCB1-deficient cancers, including combination therapies, and supports further investigation toward future translational applications."

Journal • Oncology • Rhabdoid Tumor • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SLC7A11 • SMARCB1

Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Mar 2032 ➔ Oct 2032 | Trial primary completion date: Mar 2032 ➔ Oct 2032

Trial completion date • Trial primary completion date • Cervical Cancer • Oncology • Solid Tumor

Wogonin-derived chemotype enables discovery of novel GLS1 inhibitors with potent antitumor activity. (PubMed, Future Med Chem) - "In A549 xenografts, LX-191 achieved 50.3% tumor growth inhibition at 10 mg/kg, outperforming CB-839 (21.6%) under identical conditions...The findings establish LX-191 as a promising flavone-based, non-BPTES lead for GLS1 inhibition, exhibiting multi-pathway antitumor activity both in vitro and in vivo. This work provides a tractable lead compound for the development of next-generation GLS1 therapeutics."

Journal • Oncology • STAT3

Glutaminase 1 in Vascular Disease: Linking Metabolic Reprogramming to Atherosclerosis Progression and Stability. (PubMed, J Cardiovasc Transl Res) - "We propose precision use of GLS1 modulation: a proof-of-concept strategy is short-term telaglenastat (CB-839) after angioplasty to curb neointimal hyperplasia, guided by glutamine-PET and biomarkers to avoid destabilizing mature plaques. GLS1 emerges as a tunable metabolic checkpoint whose effects depend on cell state and disease stage; judicious, time-limited modulation could complement lipid-lowering and anti-inflammatory therapies in cardiovascular disease."

Journal • Review • Atherosclerosis • Cardiovascular

Killing cancer cells by suicidal bombing attack with neutrophil extracellular traps (AACR-IO 2026) - "We have completed a phase II clinical trial of the combination of CB-839 and capecitabine, an oral prodrug of 5-FU, in PIK3CA mutant metastatic CRC patients who were refractory to prior 5-FU treatment...Lastly, we found that a variety of other chemotherapy drugs, including camptothecin/irinotecan, gemcitabine, daunorubicin, epirubicin, oxaliplatin, and regorafenib, also induced NETs, suggesting that NET induction may be a general mechanism by which chemotherapy inhibits tumor growth...In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B074."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • CTSG • CXCL8 • PIK3CA

Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities. (PubMed, Mol Biomed) - "Encouragingly, agents such as the fatty acid synthase inhibitor TVB-2640 and the glutaminase inhibitor CB-839 have already entered clinical trials. We recognize that adverse effects on normal tissues and drug resistance driven by metabolic plasticity represent major challenges for metabolism-targeted therapies. Accordingly, we systematically summarize innovative strategies that offer new therapeutic possibilities, including targeting multiple metabolic pathways through combination therapy to enhance efficacy, combining metabolic inhibitors to overcome resistance to conventional anticancer agents, leveraging metabolic reprogramming for early cancer detection, and exploring emerging approaches such as immunometabolism and metabolomics."

Journal • Review • Hepatocellular Cancer • Oncology • Solid Tumor • ATF4 • FASN • HIF1A • MYC • TCF4

Unraveling PDAC Diversity: Discovery of a metabolic distinct subtype reveals framework for tailored treatment approach (DKK 2026) - "Importantly, pharmacologic inhibition with the clinical-stage agents 9-ING-41 and the glutaminase inhibitor CB-839 significantly impairs tumor growth, with combined inhibition most effective compared to single-agent treatments and preventing the development of resistance. NFATc1high defines a new PDAC subtype while exploiting the associated glutamine addiction offers an opportunity for precision-targeted therapy in a subtype resistant to conventional treatments. The authors declare no conflict of interest."

Late-breaking abstract • CNS Disorders • Metabolic Disorders • Pancreatic Ductal Adenocarcinoma • NFATC1

Design, synthesis and biological evaluation of symmetric thiadiazole carboxamide derivative as glutaminase inhibitor. (PubMed, Bioorg Med Chem Lett) - "Although allosteric GLS inhibitors such as BPTES (Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide) and later-generation analogs such as CB-839 (Telaglenastat) have pharmacologically validated this target, their clinical utility has been constrained by suboptimal drug-like properties, including poor solubility and bioavailability...This biochemical potency translated to a functional effect in a cellular model of glutamine dependence, as evidenced by a significant depletion of intracellular glutamate pools in LDK378-resistant (LR) cells. Furthermore, TRG-192 demonstrated a favorable preclinical safety profile in initial toxicological assessments. Collectively, these data-encompassing potent target engagement, functional on-target activity, and preliminary safety-provide a compelling rationale for the advancement of TRG-192 into in vivo efficacy studies."

Journal • Oncology • KEAP1 • KRAS

Genomic alterations and their correlation with metabolic-related genes in lung cancer. (PubMed, Clin Transl Oncol) - "Rational combination strategies that pair genomic-targeted agents (sotorasib and adagrasib) with metabolic inhibitors (CB-839 and TVB-2640) show promise in overcoming adaptive resistance. Integrating genomic and metabolic profiling may enhance precision oncology approaches and improve clinical outcomes."

Journal • Review • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • EGFR • KRAS • STK11 • TP53

Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial. (PubMed, JAMA Oncol) - P2 | "A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy...Tela + Cabo was well tolerated with AEs consistent with the known risks of both agents. ClinicalTrials.gov Identifier: NCT03428217."

Clinical • Journal • Cardiovascular • Genito-urinary Cancer • Hypertension • Immune Modulation • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor

A phase I/II study of the safety and efficacy of telaglenastat (CB-839) in combination with nivolumab in patients with metastatic melanoma, renal cell carcinoma, and non-small-cell lung cancer. (PubMed, ESMO Open) - "Telaglenastat in combination with nivolumab was generally well tolerated. The combination did not show a pattern of efficacy across different study cohorts."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

CB-839 HCl in Combination With Carfilzomib and Dexamethasone in Treating Patients With Recurrent or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jan 2026 ➔ Jun 2026 | Trial primary completion date: Jan 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Momordin Ic suppresses breast cancer growth by targeting ACTL8‑dependent glutamine metabolism and PI3K/AKT/mTOR-MYC. (PubMed, Biochem Pharmacol) - "Together, these findings establish ACTL8 as a key oncogenic driver of BC progression. Targeting ACTL8 offers a novel strategy to disrupt glutamine-dependent metabolic reprogramming, and Momordin Ic represents a promising lead agent to combat ACTL8-driven BC."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • MYC • SLC1A5

A Dual Glutathione-Depleting Nanoparticle Loaded with Porcine Pancreatic Elastase for Neoadjuvant Chemotherapy of Triple Negative Breast Cancer. (PubMed, ACS Nano) - "To address the limited therapeutic potential of PPE, we constructed PMC@HA nanoparticles by coencapsulating PPE within a bimetallic Cu/Zn nanocarrier and integrating the glutaminase inhibitor CB-839...When applied as a neoadjuvant regimen in conjunction with surgery, PMC@HA significantly decreases postoperative recurrence and distant metastasis in TNBC. This combinatorial approach may improve chemosensitivity and limit metastatic progression, thereby potentially extending long-term survival in patients with TNBC."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ELANE • FAS

Telaglenastat Plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 ENTRATA Trial. (PubMed, Clin Cancer Res) - P2 | "TelaE was well tolerated and improved PFS vs PboE in patients with mRCC previously treated with TKIs and checkpoint inhibitors."

Clinical • Journal • P2 data • Cough • Fatigue • Genito-urinary Cancer • Hematological Disorders • Oncology • Pulmonary Disease • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor

Targeting glutamine metabolism and EGFR in RAS wildtype colorectal cancer (ESMO-GI 2023) - P1/2 | "We would also like to acknowledge support from Calithera Biosciences who supplied CB-839 for the study.Background: Alterations in glutamine metabolism have been proposed to play critical roles in cancer cell growth and survival. Panitumumab and CB-389 was very tolerable with some efficacy in heavily pre-treated patients. Early analysis of PET imaging data suggests a potential relationship between 18F-FSPG uptake and response, but additional studies are needed. It is anticipated that RNA-seq will identify genes that are related to glutamine avidity and represent a key determinate of response to inhibitors of glutamine metabolism."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • RAS

Ampelopsin preserves glutamate homeostasis against cerebral ischemia. (PubMed, Biomed Pharmacother) - "Notably, Amp regulates GLS, which is also the established target of CB-839, a potent and specific inhibitor known to suppress tumorigenesis...Simultaneously, NMDAR expression was reduced, preventing excitatory neurotoxicity driven by excessive glutamatergic signaling. Overall, this study highlights the potential of Amp in providing neuroprotection in mice subjected to transient focal cerebral ischemia by promoting the dynamic Glu homeostasis."

Journal • Cardiovascular • CNS Disorders • Oncology

A novel pan class-I glucose transporter inhibitor DRB18 exhibits synergistic effects with paclitaxel in vitro and in vivo against human non-small cell lung cancer. (PubMed, bioRxiv) - "Combined with different clinical and pre-clinical anticancer compounds such as V9302, CB839, Sutent, Brigatinib, DRB18 significantly increased death of A549 and Panc1 cells. Mechanistically, DRB18 treatment with paclitaxel elevated the expression of Caspases 3 and 9, suggesting GLUT-inhibiting and apoptosis-inducing anticancer mechanisms of DRB18 with paclitaxel. Collectively, our results demonstrate anticancer efficacy of pan class-I GLUT inhibitor DRB18 in combination with paclitaxel, providing a potentially more efficacious therapeutic strategy for treating advanced NSCLC and other cancers."

Journal • Preclinical • Cervical Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CASP9 • SLC2A1 • SLC2A3

Multi-omics reveals immune features in immune and non-immune cells, an IFN-γ/IFN-α-B2M positive feedback loop, and targeted metabolic therapy in multiple myeloma (ASH 2025) - "This multi-omics study delineates the complex cellular architecture of the MM TME, uncovers a novel IFN-γ/IFN-α–B2M positive feedback loop central to immune evasion and disease progression, and identifies CB-839+EGCG as a promising metabolic therapy. Our atlas provides a comprehensive resource for elucidating MM pathogenesis and tailoring targeted immunometabolic interventions."

Immune cell • IO biomarker • Hematological Malignancies • Multiple Myeloma • B2M • BCL2 • CD8 • GLS1 • IFNA1 • IFNG • IL6 • KRAS • LDHA • STAT3

Immunotherapy resistant ALL cells exhibit selective dependence on glutamine and specific transporters for growth and survival (ASH 2025) - "Introduction: Acute lymphoblastic leukemia (ALL) needs newer therapeutic options, especially in patientsthat fail targeted immunotherapies such as CD19 CART and blinatumomab...Treatmentwith the glutaminase inhibitor CB-839 sensitized resistant cells, consistent with their enhanced relianceon glutamine for energy production... CD19 immunotherapy resistant ALL cells exhibit increased expression of both glutaminaseand specific glutamine transporter SLC38A1. Our findings suggest that CD19 immunotherapy resistantcells are dependent on glutamine as a source of cellular energy. Further, our data suggests thatglutamine is selectively utilized for cellular energy in resistant cells, while it is shunted toward additionalpathways in parental cells, including the formation of asparagine and glutathione."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • CD19 • CD22