navitoclax (ABT 263) / AbbVie - LARVOL DELTA

Evaluating the Addition of Low-Dose Navitoclax to Single-Fraction Radiation Therapy Using Patient-Derived Solid Tumor Organoids and Fibroblast Co-Culture Models (ASTRO 2026) - "Our findings suggest that ABT-263 can function as a RS in a tumor type- and context-dependent manner, supporting further investigation in physiologically relevant organoid models."

Germ Cell Tumors • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Comparative Efficacy of Drug Therapies on Spleen Size and Symptom Reduction in Myelofibrosis: A Frequentist Network Meta-Analysis (SOHO 2026) - "Single-agent JAKis demonstrated variable efficacy similar to or worse than that of ruxolitinib, with an OR of 0.88 (95%CI:0.58–1.34) for momelotinib, 0.52 (95% CI, 0.05–6.05) for fedratinib, 0.35 (95% CI, 0.04–3.20) for bezacitinib, 0.17 (95% CI, 0.02–1.41) for jaktinib, and 0.16 (95% CI, 0.02–1.52) for pacritinib...Compared with BAT, pacritinib showed an OR of 3.43 (95% CI, 0.39–29.76), navtemadlin 3.26 (95% CI, 0.92–11.53), and momelotinib 3.10 (95% CI, 1.13–8.53)... In JAKi-naïve myelofibrosis, combination strategies with navitoclax or pelabresib added to ruxolitinib demonstrated the greatest spleen responses. Ruxolitinib remains similar or superior to single-agent JAKis in spleen or symptom response. In ruxolitinib-exposed patients with myelofibrosis, fedratinib, momelotinib, and pacritinib showed clinically meaningful activity compared with BAT, and fedratinib was numerically better than others."

Retrospective data • Myelofibrosis • Oncology

Identification of anoikis-related and cell matrix adhesion genes in the progression of colon adenocarcinoma using bioinformatics analysis. (PubMed, Comput Methods Biomech Biomed Engin) - "High-risk patients were more sensitive to afatinib, osimertinib, and navitoclax; low-risk patients to paclitaxel, docetaxel, and gemcitabine. These genes may serve as prognostic biomarkers and guide tailored COAD therapy."

Journal • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • BST2 • HOTAIR

Senolytics for Cancer treatment: complexities and opportunities. (PubMed, Expert Opin Ther Targets) - "Senolytic translation is constrained by TIS heterogeneity generating resistant subpopulations, potential proliferative recovery, senolytic-associated adverse effects, inability to spare beneficial senescent cells, and absence of validated clinical trial designs. Emerging immune-based strategies nanovaccines, nano-antigen-presenting machinery, and CAR-T platforms offer more selective alternatives, but require validated preclinical and clinical testing for further implementation."

Journal • Oncology

TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis. (PubMed, Blood) - P3 | "NAV+RUX showed higher hematologic toxicity versus PBO+RUX (Grade 3/4 thrombocytopenia: 54.0% vs 19.2%; Grade 3/4 neutropenia: 40.3% vs 8.8%); diarrhea (any grade: 41.9% vs 16.8%) was also more common. Cytopenias were generally manageable and reversible with dose adjustments."

Journal • P3 data • Hematological Disorders • Myelofibrosis • Neutropenia • Oncology • Thrombocytopenia

Simultaneous induction of differentiation and senescence in cardiac fibroblasts by TGF-β1: effects of senotherapeutics drugs. (PubMed, Front Pharmacol) - "Given that TGF-β1 is a central mediator of CF-to-CMF differentiation and can induce senescence in various cell lines, we investigated whether it simultaneously triggers both processes in neonatal rat CFs, and whether the senotherapeutics Navitoclax and Dasatinib + Quercetin modulate the viability of senescent CMFs. TGF-β1 simultaneously promotes CF differentiation into CMFs and induces senescence, resulting in a sustained pro-fibrotic and inflammatory phenotype. Senotherapeutics treatment attenuates senescent CMFs, supporting its potential as a therapeutic strategy to mitigate cardiac fibrosis."

Journal • Cardiovascular • Fibrosis • Immunology • Inflammation • CDKN1A • IL10 • IL1B • IL5 • IL6 • RB1 • TGFB1 • VCAM1

Preclinical Evaluation of Combined Polo-like Kinase 1 Inhibition and Navitoclax in Experimental Models of Lung Cancer. (PubMed, Int J Mol Sci) - "Using Lewis lung carcinoma (LLC1) cells, we evaluated the effects of BI2536 (a PLK-1 inhibitor) and Navitoclax, alone or in combination, in vitro and in male C57BL/6J mice using three lung cancer models: subcutaneous, intranasal, and intrapulmonary. Together, these findings indicate that while PLK-1 inhibition exerts antitumor effects in certain in vivo contexts, the therapeutic synergy observed in vitro with Navitoclax does not consistently translate to in vivo lung cancer models. This study highlights the challenges of translating combinatorial mitotic and apoptotic targeting strategies into effective in vivo therapies and underscores the importance of model selection and tumor microenvironment in preclinical drug evaluation."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • PLK1

Transform-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis (ASH 2023) - P2, P3 | "This first randomized trial in JAKi-naïve MF with NAV + RUX combination led to an SVR35W24 rate that was twice as high as PBO + RUX (P<0.0001). The responses were durable; AEs of thrombocytopenia and anemia were common but manageable with dose modification without any clinically significant sequalae. Additional evaluation is ongoing."

Clinical • Combination therapy • P3 data • Anemia • B Cell Lymphoma • Fatigue • Fibrosis • Hematological Disorders • Immunology • Leukemia • Lymphoma • Myelofibrosis • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia • Thrombocytosis • BCL2 • BCL2L1 • BCL2L2

Preclinical Studies Demonstrating Efficacy of Tasquinimod in Models of Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase (ASH 2023) - "Additionally, our findings showed that co-treatment with TM (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax induced synergistic lethality in advanced MPN-BP cells exhibiting delta synergy scores of >1.0 (by the ZIP method). In a separate experiment on the same PDX model, treatment with TM (30 mg/kg/day) also induced significantly greater survival advantage than treatment with ruxolitinib (30 mg/kg/day) or OTX015 (30 mg/kg/day) by oral gavage. These findings clearly demonstrate preclinical efficacy of TM in advanced MPN-BP cellular models and create the rationale to further interrogate the efficacy of TM alone and in combinations with current, front-line therapies for advanced MPN with excess blasts."

IO biomarker • Metastases • Preclinical • Fibrosis • Immunology • Inflammation • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1 • CALR • CCND1 • CD123 • CD33 • CD34 • CD99 • CDK6 • CDKN1A • CLEC12A • CXCR4 • IL3RA • IL6 • ITGAM • JAK2 • MPO • MYC • NLRP3 • S100A8 • S100A9 • TERT • TLR4 • TNFA

Genome-wide CRISPR screens identify an RXR-MYLIP-LDLR axis regulating BH3 mimetic sensitivity in peripheral T-cell lymphomas. (PubMed, Oncogene) - "MYLIP deletion enhanced the cytotoxicity of navitoclax, venetoclax, and the BCL-XL-selective degrader DT2216 across multiple PTCL models. Transcriptomic analyses of primary PTCL samples revealed reduced MYLIP expression in ALK-positive anaplastic large cell lymphoma and genetically defined subsets of nodal T follicular helper cell lymphomas. These findings uncover an RXR-MYLIP-LDLR axis that links cholesterol metabolism to apoptotic susceptibility, offering mechanistic insight into BH3 mimetic sensitivity in PTCL."

Journal • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • ALK • BCL2L1 • LDLR • RXRB

Superior Preclinical Efficacy of BRG1/BRM Inhibitor Combined With BET Inhibitor or Decitabine Against MECOM-rearranged (MECOM-r) Acute Myeloid Leukemia (AML) (SOHO 2025) - "Taken together, these findings highlight the promise of FHD-286– based rational combinations, especially with BETi, navitoclax, or decitabine, in exerting significant anti-AML efficacy against cellular models of MECOM-r AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CD93 • CDK4 • GATA2 • ITGAM • KIT • MECOM • MYC • PLK1 • SMARCA4

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. (PubMed, Cancer Discov) - P1 | "Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population."

Clinical • Combination therapy • Journal • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • Thrombocytopenia • Transplantation

NAVITOCLAX PLUS RUXOLITINIB IN JAK INHIBITOR-NAÏVE PATIENTS WITH MYELOFIBROSIS: PRELIMINARY SAFETY AND EFFICACY IN A MULTICENTER, OPEN-LABEL PHASE 2 STUDY (EHA 2022) - P2 | "Conclusion The combination of navitoclax and ruxolitinib was well tolerated and demonstrated early and robust reductions in spleen volume, anemia, and BM fibrosis in patients without prior JAK-2 inhibitor exposure. SVR 35, anemia, and bone marrow fibrosis improved over time."

Clinical • P2 data • Anemia • Cardiovascular • Hematological Disorders • Immunology • Myelofibrosis • Neutropenia • Thrombocytopenia • BCL2 • BCL2L1

Addition of Navitoclax to Ongoing Ruxolitinib Therapy for Patients With Myelofibrosis With Progression or Suboptimal Response: Phase II Safety and Efficacy. (PubMed, J Clin Oncol) - P2 | "The addition of navitoclax to ruxolitinib in patients with persistent or progressive myelofibrosis resulted in durable SVR, improved TSS, hemoglobin response, and BMF. Further investigation is underway to qualify the potential for disease modification."

IO biomarker • Journal • P2 data • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • BCL2L1

Randomized phase II trial of dabrafenib and trametinib with or without navitoclax in patients (pts) with BRAF-mutant (MT) metastatic melanoma (MM) (CTEP P9466). (ASCO 2023) - P1/2 | "In pts with BRAF MT MM, DTN was associated with a CR rate of 20% and ORR of 84%. There was a trend for improved OS in pts treated with DTN compared to DT; the difference in OS was significant in pts with smaller tumor burden. The DTN regimen may be considered for further exploration in the post-ICI setting."

Clinical • IO biomarker • Metastases • P2 data • Fatigue • Immune Modulation • Melanoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • BCL2L2 • BRAF

Dasatinib overcomes AML cells resistant to BCL2 inhibition by degrading MCL1. (PubMed, Br J Haematol) - P=N/A | "Venetoclax (VEN) combined with azacitidine has changed the paradigm of treatment of AML...We noticed that 17 (15.7%) were navitoclax-resistant (NAV-R)...Collectively, these results suggest that DASA degrades MCL1 and effectively kills AML cells. To prove this hypothesis, we designed a phase II clinical trial named VEN-R DASA-IPC 2022 067 (EUCT 2023-505846-24-00), currently enrolling VEN-R patients."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • CASP3 • MCL1

Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study. (PubMed, Lancet Haematol) - P2 | "These biomarker analyses reveal clinically meaningful splenic responses independent of high molecular risk mutation status in patients treated with navitoclax plus ruxolitinib who were not benefiting from ruxolitinib monotherapy. Furthermore, the overall survival benefit observed in those with an improvement in fibrosis or a reduction in variant allele frequency is suggestive of disease modification, implying the therapeutic potential of adding navitoclax to ruxolitinib for patients with myelofibrosis who had disease progression or suboptimal response to ruxolitinib monotherapy."

Biomarker • Journal • P2 data • Retrospective data • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • TIMP1 • VCAM1

Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE). (PubMed, Hematol Oncol) - P2 | "These findings suggest navitoclax plus ruxolitinib has a tolerable safety profile and provides clinically meaningful improvements for JAKi-naïve patients with myelofibrosis. TRIAL REGISTRATION: NCT03222609."

IO biomarker • Journal • P2 data • B Cell Lymphoma • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Lymphoma • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology

The Combination of Navitoclax and Ruxolitinib in JAK Inhibitor-Naïve Patients with Myelofibrosis Mediates Responses Suggestive of Disease Modification (ASH 2022) - P2 | "Among JAKi treatment-naïve patients with MF, the combination of navitoclax and ruxolitinib reduced splenomegaly in several high-risk groups known to confer poor prognosis. Reductions in BMF and VAF were independent of HMR mutations. The reduction in BMF and VAF for the driver mutation JAK2V617 is encouraging and suggestive of evidence of disease modification with the combination of navitoclax and ruxolitinib."

Clinical • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • ASXL1 • CALR • IDH1 • IDH2 • JAK2 • SRSF2 • U2AF1

Tumor immunosenescence drives breast cancer progression and therapeutic resistance: mechanisms and emerging interventions. (PubMed, Front Oncol) - "Finally, we evaluate emerging interventions-senolytics (navitoclax, dasatinib plus quercetin, fisetin), senomorphics, metabolic rescue via NAD+ repletion, STING agonists, and rational senotherapy-immunotherapy combinations-emphasizing that most remain at preclinical or early clinical stages. We conclude that targeting tumor immunosenescence represents a promising but incompletely validated therapeutic axis for enhancing anti-tumor immunity in breast cancer."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • CAFs • CXCL8 • HER-2 • IL6 • TGFB1

Addition of navitoclax to ruxolitinib mediates responses suggestive of disease modification in patients with myelofibrosis previously treated with ruxolitinib monotherapy (AACR 2022) - P2 | "These responses are suggestive of disease modification asthey were associated with improved OS for patients. In addition, the NAV plus RUX regimen potentially improved the outcome for patients with MF regardless of HMR status."

Clinical • IO biomarker • Late-breaking abstract • Monotherapy • Myelofibrosis • Oncology • ASXL1 • BCL2L1 • CALR • IDH1 • IDH2 • JAK2 • SRSF2 • U2AF1

A clinically translatable next-generation EVA strategy for glioblastoma: combining eltanexor and BH3-mimetics drives synergistic apoptosis. (EANO 2026) - "Background:Glioblastoma (GB) is characterized by marked aggressiveness, poor clinical outcome, and rapid development of resistance to currently available treatments. Replacing the original Venetoclax/A1210477 backbone with Navitoclax and a clinically advanced MCL-1 inhibitor resulted in substantially enhanced anti-glioblastoma activity and robust synergistic effects, with MIK665 showing superior performance compared with S63845 across experiments. These data support further development of Navitoclax and MIK665 as core components of a next-generation EVA strategy with strong translational potential."

Clinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BCL2 • BCL2L1 • BCL2L2 • CASP3

Evaluation of the Lethal Activity and Its Mechanism of Tasquinimod in Advanced Myeloproliferative Neoplasm (MPN) in Blastic Phase (ASH 2024) - "Importantly, cotreatment with TQ (5 to 30 µM) and ruxolitinib (250 to 1000 nM), BET inhibitor OTX015 (50 to 250 nM) or pelabresib (CPI-0610) (100 to 500 nM), or BCL2/Bcl-xL inhibitor navitoclax, induced synergistic lethality in advanced MPN-BP cells, represented by delta synergy scores of >1.0 (by the ZIP method)...Co-treatment with TQ and RGFP966 (HDAC3i) induced synergistic lethality in post-MPN sAML cells...These findings demonstrate the pre-clinical efficacy of TQ and/or JAKi or BETi or with novel agents identified here in advanced MPN and MPN-AML cells. They also create the rationale to further interrogate the pre-clinical efficacy of the TQ-based combinations against cellular models of advanced MPN."

IO biomarker • Metastases • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • BCL2 • BCL2L1 • CALR • CCL2 • CCND1 • CD123 • CD33 • CD34 • CD99 • CDK6 • CDKN1A • CLEC12A • CXCL12 • CXCL8 • CXCR4 • HDAC3 • IL1A • IL3RA • IL6 • ITGAM • JAK2 • MPO • MYC • NLRP3 • NSD2 • S100A8 • S100A9 • TERT • TLR4 • TNFA • TP53

BH3-mimetic drugs elicit cell death of neuroendocrine tumours in preclinical models – An emerging therapeutic strategy for NETs (ENETS 2025) - "MATERIALS AND METHODS NET patient-derived organoids (PDOs) were established from fresh surgical surplus NET tissue samples and treated with combinations of BH3-mimetics and SOC (Sunitinib, Cabozantinib, Everolimus, and 177Lu-Dotatate)...Finally, we show that combining Navitoclax with Cabozantinib or 177Lu-Dotatate results in marked cell death of NETs, while the single treatments exhibited a significantly lower effect. CONCLUSION Overall, this study showed that the survival of NETs depends on the activity of the Bcl-2 family of proteins and that their inhibition using BH3-mimetics combined with the SOC leads to cell death in patient-derived preclinical models. Our data warrant the investigation of BH3-mimetics with the SOC for patients with NETs as a novel therapeutic approach."

IO biomarker • Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • BCL2 • BCL2L1 • MCL1

SEQUENTIAL CISPLATIN –NAVITOCLAX THERAPY EXPLOITS AN ADAPTIVE VULNERABILITY IN EPITHELIAL OVARIAN CANCER (IGCS 2026) - "CRISPR screening identified genes with antagonistic pleiotropy across chemotherapeutic conditions, with the strongest overlap between cisplatin and navitoclax. Residual EOC cells after cisplatin treatment showed increased sensitivity to navitoclax, whereas navitoclax pretreatment did not affect cisplatin response. This effect was most evident during early adaptation and decreased with resistance."

Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor