buparlisib (AN2025) / Novartis, Adlai Nortye, Nippon Kayaku - LARVOL DELTA

Updated meta-analysis of inhibitor development in previously untreated patients with severe Hemophilia A: Plasma-derived versus recombinant FVIII products (ASH 2025) - "Asystematic literature search was performed using PubMed for studies published between 2000 and2025...Five studies comprising a total of 3,236 patients (758 treated with plasma-derived FVIII and 2,478 withrecombinant FVIII) were included in the meta-analysis. Using a random-effects model (REML) based on amanually calculated log risk ratios and standard errors, the pooled analysis demonstrated a significantlylower risk of inhibitor development in patients receiving pdFVIII compared to those receiving rFVIII. Thepooled risk ratio (RR) was 0.74, with a 95% confidence interval (CI) of 0.57 to 0.96 (p = 0.026), indicating a26% relative risk reduction associated with pdFVIII."

Retrospective data • Hematological Disorders • Hemophilia • Hemophilia A • Rare Diseases

Longitudinal trends in vaccination and cancer screening engagement among patients with chronic lymphocytic leukemia: A prospective cohort study and quality improvement initiative (2019–2025) (ASH 2025) - "Influenza vaccination rates were 92% in2020 and 95% in 2021, declined to 74% in 2022, 66% in 2023, 62% in 2024 and increased to 67% in 2025(2025 vs. 2020 OR = 0.18, 95% CI: 0.02–1.51, p = 0.027); pneumococcal vaccination rates were 58% in2020, 79% in 2021, declined to 63% in 2022, 42% in 2023, 37% in 2024 and 33% in 2025 (2025 vs. 2020 OR= 0.37, 95% CI: 0.09–1.39, p = 0.037); Shingles vaccination started at 20% in 2020, increased to 55% in2021 (OR = 4.89, p = 0.018), decreased to 47% in 2022, 37% in 2023, 39% in 2024, and 34% in 2025.COVID-19 vaccination was 33% in 2021, peaked at 80% in 2022, declined to 56% in 2023, 48% in 2024 and2025 (2025 vs. 2022 OR = 0.23, 95% CI: 0.09–0.58, p = 1.9 × 10⁻⁵)...However,administering repeated yearly surveys was associated with improved uptake over time, includingrecovery of mammography and colonoscopy rates by 2025 and increased rates of dermatology visits andPSA screening. These findings highlight the importance of..."

Clinical • Chronic Lymphocytic Leukemia • Dermatology • Hematological Malignancies • Herpes Zoster • Infectious Disease • Influenza • Leukemia • Oncology • Pneumococcal Infections • Preventive care • Respiratory Diseases • Varicella Zoster

Chronic myelomonocytic leukemia: Clinical outcomes from clinical trials submitted to the FDA over the past 25 years (ASH 2025) - "Due to its rarity, clinical research inCMML has been limited, with current therapeutic approvals restricted to only three hypomethylatingagents (HMAs): azacitidine, decitabine, and decitabine/cedazuridine...To address these gaps, this study aims to evaluate overall survival (OS)outcomes and response rates across different treatment modalities and across CMML subtypes.MethodsWe searched for phase 2 and 3 trials including patients with CMML submitted to FDA as part of New DrugApplications and Investigational New Drug Applications for the treatment of MDS between 2000 and2025...We identified 10 trials evaluating 5 investigational agents for MDS treatment that included a total of 196patients with CMML. These 196 patients were categorized into three treatment groups: HMAmonotherapy (n=104), HMA combination therapy (n=63) and control (conventional care regimen orsupportive care, n=29). The study population had a median age of 70 years, was 69% male, and included85% White, 12%..."

Clinical • Clinical data • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

High event-free (EFS) and overall survival (OS) after non-total body irradiation (TBI) conditioning and allogeneic hematopoietic cell transplantation (HCT) in next-generation-sequencing minimal residual disease (NGS-MRD) negative B-acute lymphoblastic leukemia (B-ALL): Results from the EndRAD trial (PTCTC ONC1701) (ASH 2025) - P2 | "Based upon retrospectivedata showing low rates of relapse, we hypothesized that patients with negative pre-HCT MRD by next-generation-sequencing of IgH B-cell receptor rearrangements (NGS-MRD) could achieve 2-year EFSexceeding 75% with a non-TBI regimen, an outcome comparable to those receiving TBI-based regimens. The Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) conducted a phase IIprospective trial at 45 Centers in North America (ONC1701 EndRAD: NCT03509961) between 2018 and2025 to evaluate outcomes of myeloablative non-TBI conditioning regimens for allogeneic HCT in B-ALLpatients at lower risk for relapse defined by absence of NGS-MRD (Clonoseq) of B-cell receptorrearrangements (BCR) just prior to HCT...Mismatched related/haploidentical grafts received post-transplant cyclophosphamide orTCRαβ/CD19 depletion according to institutional preference...Of patientsenrolled, 33% were White/Non-Hispanic, 37% Hispanic, 12% Black or African American, and..."

Biomarker • Clinical • IO biomarker • Minimal residual disease • Next-generation sequencing • Residual disease • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Transplantation

Long-term functional drug and immunotherapy screening in immune-competent patient-derived microtissues across brain tumors (SNO 2025) - "Glioma cell line-based screens revealed inter-model variability in drug sensitivity, with only a few agents, including Pimasertib, Etoposide, Buparlisib, and Volasertib, demonstrating consistent efficacy, underscoring the need for individualized profiling. Our long-term, dynamic screening system supports personalized oncology approaches by enabling functional analysis of both drug and immune responses. Further validation in prospective clinical trials is required to determine its translational impact."

Clinical • Brain Cancer • Glioblastoma • Glioma • Meningioma • Oncology • Solid Tumor

Long-term functional drug and immunotherapy screening in immune-competent patient-derived microtissues across brain tumors (WFNOS 2025) - "Glioma cell line-based screens revealed inter-model variability in drug sensitivity, with only a few agents, including Pimasertib, Etoposide, Buparlisib, and Volasertib, demonstrating consistent efficacy, underscoring the need for individualized profiling. Our long-term, dynamic screening system supports personalized oncology approaches by enabling functional analysis of both drug and immune responses. Further validation in prospective clinical trials is required to determine its translational impact."

Clinical • Brain Cancer • Glioblastoma • Glioma • Meningioma • Solid Tumor

Computational profiling of flavonoids against key breast cancer targets: an in-silico exploration. (PubMed, In Silico Pharmacol) - "Comparative docking with five reference drugs (Alpelisib, Buparlisib, Lapatinib, Gefitinib, and Afatinib) identified nine flavonoids; Sphaerobioside, Avicularin, Nicotiflorin, Myricetin, Quercitrin, Rutin, Isoquercetin, Didymin, and Robinin as promising candidates with favorable binding affinities and stable receptor interactions...Collectively, these findings highlight the multitarget inhibitory potential of selected flavonoids and demonstrate how integrated computational profiling can accelerate the discovery and optimization of natural product-based anticancer agents. The online version contains supplementary material available at 10.1007/s40203-025-00489-0."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • EGFR • HER-2

The BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC (clinicaltrials.gov) - P3 | N=487 | Completed | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Nov 2025 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Trial completion • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Collaborative role of calcitriol with buparlisib in the tongue squamous cell carcinoma cell line by modulating the Casp3 and Akt1 gene expression. (PubMed, Dent Med Probl) - "Vitamin D represents an efficient anticancer adjuvant that permits a novel therapeutic strategy for cancer patients."

Journal • Preclinical • Oncology • Oral Cancer • Squamous Cell Carcinoma • Tongue Carcinoma • AKT1 • CASP3 • mTOR

Dasatinib Overcomes AML Resistance to BCL2 Inhibition By Indirectly Inhibiting MCL1: From Ex Vivo drug Sensitivity/Resistance Profiling to a Phase II Clinical Trial: A Hemato-BIO Study (ASH 2024) - P=N/A | "BH3 mimetics such as the BCL2 specific inhibitor (-inh) venetoclax (VEN) and the BCL2/BLCxL-inh navitoclax (NAV), are small molecules inducing intrinsic apoptotic cell death by inhibiting antiapoptotic proteins...We noticed a strong anticorrelation between NAV-R and sensitivity to most of the tested kinase inhibitors, including the Pi3K-inh BKM120 (Buparlisib) and Idelalisib, the JAK2-inh Ruxolitinib, the MEK-inh Trametinib, the mTOR-inh Temsirolimus, the FLT3-inh Quizartinib, and the BCR-ABL-inh Imatinib and Dasatinib (DASA). On the other hand, we did not observe any anticorrelation with the EGFR-inh erlotinib nor gefitinib...DASA may be efficient in targeting VEN-R by inhibiting MCL1. Preclinical studies based on the AML collections HEMATIO-BIO allowed us to ask clinical questions that can be addressed in early-phase clinical trial."

IO biomarker • P2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCL2 • BCL2L1 • BCR • EGFR • FLT3 • JAK2 • KIT • KRAS • NPM1 • NRAS • PTPN11 • TP53

Cheminformatics-based analysis identified Novel compounds from Nelumbo nucifera as potential inhibitors targeting PI3k/Akt/mTOR Pathway of HR+/HER2- subtype for Breast Cancer. (PubMed, Biochem Biophys Res Commun) - "Two lead compounds, Anonaine (CID_160597) and Dehydroaporheine (CID_161899), exhibited more binding abilities towards the PI3Kα protein than the reference inhibitor buparlisib...This research lays the groundwork for additional experimental confirmation and underscores the promise of N. nucifera products in creating effective alternative therapies against breast cancer. This research may contribute to advancing personalised medicine approaches in oncology, offering new avenues for targeted therapies in PIK3CA-mutant breast cancer."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Essential roles of mechanistic target of rapamycin in the induction of steroid resistance in group 2 innate lymphoid cells and severe asthma. (PubMed, J Pharmacol Exp Ther) - "The interleukin (IL)-33/thymic stromal lymphopoietin (TSLP)/IL-7-induced growth of group 2 innate lymphoid cells (ILC2) in vitro was resistant to dexamethasone (DEX), but suppressed by everolimus, an mTOR inhibitor, in a concentration-dependent manner...The combination of the pan-class I phosphatidylinositide-3 kinase inhibitor, buparlisib and the pan-Akt inhibitor, capivasertib also attenuated the resistance of IL-33/TSLP/IL-7-exposed ILC2s to DEX...This study demonstrates that activation of the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (mTOR) pathway induces steroid resistance in group 2 innate lymphoid cells. Targeting mTOR with everolimus restores steroid sensitivity, highlighting mTOR inhibition as a promising pharmacotherapy for steroid-resistant asthma."

Journal • Asthma • B Cell Lymphoma • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • IL33 • IL7 • mTOR • TSLP

Discovery of Novel PI3K/BRD4 Dual Inhibitors for Esophageal Cancer: Rational Design, Optimization, and Senescence-Inducing Mechanisms. (PubMed, J Med Chem) - "In vivo, 23 demonstrated anticancer efficacy comparable to that of the BKM120/JQ1 combination treatment in a KYSE450 xenograft mouse model. Significantly, the senolytic agent ABT737 enhanced the efficacy of compound 23 through the selective clearance of senescent cancer cells. Collectively, this work establishes 23 as a promising PI3K/BRD4 dual-targeting lead and supports senescence induction combined with senolytics as a novel strategy for esophageal cancer treatment."

Journal • Esophageal Cancer • Oncology • BRD4

A genetic signature predicts the response of aggressive paragangliomas to dual PI3K and CDK4/6 inhibition (ESMO 2025) - "Methods We evaluated buparlisib (PI3Kα inhibitor) and ribociclib (CDK4/6 inhibitor), alone and combined, in functional assays using in vitro PPGL models, including two rodent cell lines (MPC, PC12) and rat-/patient-derived primary PPGL cells. Given mitotic gene upregulation in mPPGL, this combination therapy may offer a promising strategy for aggressive disease. Legal entity responsible for the study The authors."

Oncology • Solid Tumor • FOXM1 • PIK3CA

Buparlisib/Chemo Combo Misses OS Mark in PD-1–Treated Recurrent HNC (Oncology Nursing News) - "Findings showed that the median OS with buparlisib plus paclitaxel was 9.6 months compared with 9.7 months with paclitaxel alone in this patient population (HR, 1.02; 95% CI, 0.83-1.26; P = .85)...Additional efficacy data showed that the confirmed ORR per IRRC was 30.3% with buparlisib/paclitaxel compared with 20.7% with paclitaxel alone (P = .024); the unconfirmed ORRs by IRRC were 44.3% and 28.0%, respectively (P = .0005). When assessed via investigator, the confirmed ORRs were 29.7% vs 24.4% (P = .22) and unconfirmed ORRs were 44.6% and 28.0% (P = .0004)."

P3 data • Squamous Cell Carcinoma of Head and Neck

BURAN: A phase III study of buparlisib (BUP) plus paclitaxel (PAC) in patients with PD-1(PD-L1)-pretreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (ESMO 2025) - P3 | "Notably, the control arm (PAC alone) demonstrated a longer OS than historically observed in the phase II BERIL-1 trial (median 6.5 mos), potentially contributing to the outcome. Subgroup analyses will be presented at the meeting."

Clinical • Late-breaking abstract • Metastases • P3 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Targeting the Phosphoinositide 3-Kinase/Protein Kinase B Pathway Suppresses Y-Box Binding Protein 1 Expression and Inhibits Colorectal Cancer Progression. (PubMed, World J Oncol) - "The impact of YBX1 on the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was evaluated, and the effects of the PI3K inhibitor buparlisib (BKM120) on YBX1-driven cellular phenotypes were also tested...This study highlights the oncogenic role of YBX1 in CRC and reveals a potential YBX1-PI3K/AKT regulatory axis that may serve as a promising therapeutic target. The findings suggest that targeting this axis could provide a novel strategy for CRC treatment, especially under hypoxic or microenvironmental stress conditions."

Journal • Colorectal Cancer • Oncology • Solid Tumor • YBX1

Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors. (PubMed, Int J Mol Sci) - "In this study, we investigated the effects of conventional chemotherapeutics, Cisplatin and 5-fluorouracil (5-FU), in combination with small molecule inhibitors (SMIs) targeting the PI3K/AKT signaling pathway, on NSCLC cell viability...Dose-response analyses were performed to determine the optimal concentrations of Cisplatin, 5-FU, the AKT inhibitor MK2206, and the PI3K inhibitor BKM120, both as monotherapies and in combination treatments...Mechanistic studies revealed that apoptosis induction was mediated through the apoptotic pathway regulated by the Bcl-2 family and activation of caspase-3 and caspase-6. These findings highlight the therapeutic potential of combining PI3K/AKT inhibitors with conventional chemotherapy to overcome resistance mechanisms in NSCLC."

Journal • Large Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL2 • CASP3 • CASP6

Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer. (PubMed, Future Med Chem) - "Current clinical research focuses on compounds such as GDC-0077 and NVP-BKM120, advancing into phase II/III clinical trials. Preclinical drugs like NVP-CLR457, AZD6482, PF-06843195, and GDC-0326 show promising potential for further optimization and entry into BC clinical trials. This review aims to provide an overview of the clinical and preclinical development of small molecule inhibitors for various molecular subtypes of BC, emphasizing their structural composition, therapeutic outcomes, and mechanisms of action. Additionally, we highlight key targets and pathways involved in BC pathogenesis, offering essential insights for the design of effective therapeutic agents for breast cancer."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Combinatorial targeting of PI3K/AKT pathway with BKM120 increases cisplatin sensitivity and apoptotic response in A549 lung cancer cells. (PubMed, Cell Mol Biol (Noisy-le-grand)) - "The effects of autophagy and proteasome inhibition were further examined using chloroquine and bortezomib, respectively. Moreover, our real-time PCR analysis provided evidence that the combination treatment not only down-regulated Bcl-2 expression but also upregulated BAD and BAX expression in A549 cells, which ultimately led to apoptotic-mediated cell death. In conclusion, this investigation illuminated the role of PI3K inhibition in the chemo-sensitivity of 549 cells and revealed that the combination of BKM120 and Cisplatin may represent a viable therapeutic option for NSCLC."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BAD • BAX • BCL2 • CDKN1A

Crosstalk between oncogenic signaling pathways as driver of therapy resistance against small molecule inhibitors in Glioblastoma (EACR 2025) - "Result and SMIs targeting downstream effector kinases (Trametinib, Buparlisib, Abemaciclib; IC50 70nM-1µM) or membrane-bound tyrosine kinase receptors (Afatinib, Capmatinib, Axitinib; IC50 1-15µM) reduced cell viability...Combined trametinib and SP600125 (JNKi) mitigated JNK/c-Jun activation and synergistically reduced cell viability (Bliss >20), but failed to suppress MEKSer221 hyperphosphorylation... Trametinib reduces cell viability but triggers compensatory signaling, including MEKSer221 hyperphosphorylation. This study presents a mechanistically driven selection of tumor-tailored combination treatments to overcome resistance to SMI monotherapy in pdGBM models, highlighting VEGFR co-inhibition as a promising combinatorial strategy with trametinib."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

A genetic signature predicts the response of aggressive paragangliomas to dual PI3K and CDK4/6 inhibition. (EACR 2025) - "In this study, we investigate the antitumor potential of targeting two key dysregulated pathways in PPGL: PI3K signaling and cell cycle regulation.Material and We assessed the efficacy of buparlisib, a PI3Kα inhibitor (PI3Ki), and ribociclib, a CDK4/6 inhibitor (CDK4/6i), as monotherapies and in combination, using functional assays in representative in vitro models of PPGL. Combined inhibition of PI3K and CDK4/6 targets mitotic spindle regulation and exerts potent antitumor effects in PPGL models. Given the upregulation of mitosis-associated genes in mPPGL, this combination therapy holds promise as a novel approach for treating aggressive forms of these tumors."

Oncology • Solid Tumor • FOXM1 • PIK3CA

DiWB-1: A Luteinizing Hormone Releasing Hormone (LHRH)-Targeted Peptide-Drug Conjugate (PDC) With Enhanced Tumor Selectivity and PI3K Inhibition Efficacy. (PubMed, Arch Pharm (Weinheim)) - "IV-6 was then conjugated to the PI3K inhibitor buparlisib, forming the target PDC, DiWB-1. Pharmacokinetic studies further indicated that DiWB-1 had favorable metabolic stability, with a half-life of 5.6 h, slightly exceeding that of triptorelin (4.2 h). These findings suggest that DiWB-1 holds promise as a selective, potent, and long-acting anticancer PDC, warranting further investigation."

Journal • Diabetes • Oncology

Double/Triple Combinations of AN2025, AN0025 and Atezolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Adlai Nortye Biopharma Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Solid Tumor

DISSECTING THE HELLS GENE SIGNATURE IN ANAPLASTIC LARGE CELL LYMPHOMA: IMPLICATIONS FOR DRUG REPURPOSING AND COMBINATION THERAPY (EHA 2025) - "To validate these results, we treated HELLSKD and control cells with IC20 dose of a representative compound of each class (BKM-120 for PI3K, Ruxolitinib for JAK1/2, AZD7648 for DNA-PK). Collectively, these findings pave the way for the development of effective and clinically translatable strategies for HELLS inhibition. Such pharmacological inhibitors hold promise not only as monotherapy but also in synergistic combination with conventional and targeted therapies"

Combination therapy • Gene Signature • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK • HELLS • IFNG • JAK1 • JAK2