afuresertib (LAE002) / Laekna Therap, Qilu Pharma - LARVOL DELTA

An Open-Label Randomized Active-Controlled Phase II Clinical Study to Assess the Efficacy and Safety of Afuresertib Plus Paclitaxel Versus Paclitaxel in Patients with Platinum-Resistant Ovarian Cancer (GOG 3044) (SGO 2025) - No abstract available

Clinical • P2 data • Oncology • Ovarian Cancer • Solid Tumor

New Drug Application for LAE002 (afuresertib) Accepted by China's National Medical Products Administration (PRNewswire) - "The NDA is supported by positive results from the Phase III Clinical Trial (AFFIRM-205) conducted in...patients with locally advanced or metastatic HR+/HER2- breast cancer (LA/mBC) with PIK3CA/AKT1/PTEN alterations, following recurrence or progression on or after endocrine therapy(-ies) (with or without a CDK4/6 inhibitor)."

China filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Study Evaluating Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients w/ Locally Advanced or Metastatic HR+/HER2- Breast Cancer (clinicaltrials.gov) - P3 | N=256 | Recruiting | Sponsor: Laekna Limited | Active, not recruiting ➔ Recruiting | Phase classification: P1 ➔ P3 | N=20 ➔ 256 | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Apr 2023 ➔ Oct 2026

Enrollment change • Enrollment open • Metastases • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • HER-2 • PIK3CA • PTEN

Study Evaluating Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients w/ Locally Advanced or Metastatic HR+/HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Laekna LLC | Trial primary completion date: Sep 2022 ➔ Jan 2023

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

Study Evaluating Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients w/ Locally Advanced or Metastatic HR+/HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Laekna LLC | Trial primary completion date: Jan 2023 ➔ Jun 2023

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • PTEN

AKT1 glutarylation regulated by GCDH and SIRT5 suppresses oncogenic signaling. (PubMed, Cell Rep) - "Notably, pharmacological MYC inhibition, which downregulates GCDH and elevates AKT1 glutarylation, synergizes with the AKT inhibitor afuresertib to suppress gastric cancer cell growth, revealing a potential therapeutic vulnerability. These findings link lysine metabolism to AKT-driven cancer progression and suggest therapeutic strategies targeting glutarylation dynamics."

Journal • Gastric Cancer • Oncology • Solid Tumor • AKT1 • SIRT5

Integrated analysis of programmed cell death-related genes identifies CORO1A as an apoptosis-associated gene in acute myeloid leukemia. (PubMed, PeerJ) - "OncoPredict suggested higher sensitivity in the high-risk group to 5-fluorouracil, PI3K-AKT-mTOR inhibitors (afuresertib, pictilisib, taselisib, dactolisib), and the MET inhibitor savolitinib. Multi-omic integration of PCD-related genes delineates PCD-driven heterogeneity in AML and yields a robust five-gene prognostic model with therapeutic implications. CORO1A emerges as a potential apoptosis-associated oncogene that promoting AML cell survival."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • BCL2 • CD31 • CORO • CXCR3 • IL10 • ITGA4 • PECAM1 • PPBP

Gene knockout or selective inhibition of AKT-3, but not AKT-1 or AKT-2 isoform, enhances apoptosis in CD133+ melanoma cancer stem cells treated with the MEK inhibitor trametinib (AACR 2026) - "Combinational inhibition of the MAPK and PI3K/AKT pathways with trametinib and the pan-AKT inhibitor capivasertib synergistically induces melanoma cell apoptosis in vitro and inhibits tumor growth in vivo...We next investigated apoptosis induction by selective inhibitors of each of the AKT isoforms; afuresertib for AKT-1, CCT128930 for AKT-2, or uprosertib for AKT-3, as a monotherapy or in combination with trametinib...Future studies will focus on optimizing the effect of selective inhibitors of AKT-3 in dose response experiments, and test its effects in in vivo mouse xenograft studies. Simultaneously targeting the AKT and MAPK survival pathways with trametinib and uprosertib underscores the importance of combination therapies to eliminate recalcitrant melanoma stem cells."

Cancer stem • Brain Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor • AKT1 • AKT2 • ANXA5 • CD133 • NRAS

Laekna…is pleased to announce that LAE002 (afuresertib) plus fulvestrant has demonstrated strong positive topline results in the phase III clinical trial in locally advanced or metastatic HR+/HER2- breast cancer ('LA/mBC') patients with PIK3CA/AKT1/PTEN alterations, following recurrence or progression on or after endocrine therapy(-ies) (with or without a CDK4/6 inhibitor)... (HKEXnews) - "A total of 261 subjects were enrolled and 70.5% of subjects were previously treated with CDK4/6 inhibitors. The study met its primary endpoint with a median PFS of 7.6 months for LAE002 (afuresertib) plus fulvestrant combination versus 2.0 months for placebo plus fulvestrant, HR=0.33 (p-value <0.0001). Treatment with oral, once-daily LAE002 (afuresertib) was well tolerated....The detailed study results will be presented at an upcoming international scientific conference...The Group will work together with Qilu Pharmaceutical Company Limited ('Qilu Pharma') to submit the new drug application ('NDA') for LAE002 (afuresertib) to the Center for Drug Evaluation ('CDE') of China’s National Medical Products Administration ('NMPA') in the near term."

China filing • P3 data: top line • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Study to Evaluate Efficacy & Safety of Afuresertib Plus Fulvestrant in Patients With Locally Advanced or Metastatic HR+/HER2- Breast Cancer (clinicaltrials.gov) - P3 | N=256 | Active, not recruiting | Sponsor: Laekna Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

Phase I/II clinical trials of LAE005, afuresertib plus nab-paclitaxel in patients with advanced solid tumors, primarily in patients with triple-negative breast cancer (TNBC) (AACR 2024) - P1 | "The triplet regimen shows a manageable safety profile and encouraging preliminary activity in the drug resistant TNBC patients. This triplet regimen warrants further investigation."

Clinical • Metastases • P1/2 data • Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Afuresertib plus fulvestrant for pretreated HR-positive, HER2-negative, advanced breast cancer: a phase Ib trial. (PubMed, Nat Commun) - P3 | "In conclusion, afuresertib plus fulvestrant was well-tolerated and had promising antitumor activities against pretreated, advanced HR-positive, HER2-negative breast cancer, supporting further studies with randomized controlled trials. This trial is registered with ClinicalTrials.gov (NCT04851613)."

Journal • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Organoid platinum-resistance model identifies KRT17 as a biomarker of targeted therapy in ovarian cancer. (PubMed, iScience) - "To study resistance mechanisms, we developed the organoid drug resistance assay (ODR-test) with patient-derived organoids from our ovarian cancer biobank and identified sustained phenotypic reprogramming and cellular plasticity of organoids under carboplatin pressure as a conserved mechanism irrespective of the basal resistance level. Additionally, we found that KRT17 expression status (K-score) is a significant negative prognostic histopathological biomarker in a large cohort (N = 384) of patients with advanced HGSOC. In organoids, increased KRT17 levels enhanced sensitivity to PI3K/Akt inhibitors alpelisib and afuresertib, highlighting the potential of KRT17 as a stratification biomarker for targeted therapies."

Biomarker • Journal • Platinum resistant • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • KRT17

Anti-tumour and associated metabolic effects of repurposed afuresertib and taxifolin for glioblastoma treatment. (PubMed, Analyst) - "Afuresertib could affect amino acid metabolism and glycerophospholipid metabolism, exerting the function of anti-proliferation and anti-invasion. Taxifolin could damage nicotinate and nicotinamide metabolism, leading to the death of tumour cells."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor

Afuresertib +Sintilimab+Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1 (clinicaltrials.gov) - P1/2 | N=22 | Completed | Sponsor: Laekna Limited | Active, not recruiting ➔ Completed

Trial completion • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • HER-2 • KRAS • PI3K • PTEN

Inhibition of AKT or mTOR molecules mitigates obesity-associated metabolic disorders in Riz1-/- mice with obesity. (PubMed, Biomed Pharmacother) - "Riz1 knockout mice (KO) were randomly treated with either the AKT inhibitor afuresertib or the mTOR inhibitor rapamycin. Mice treated with the inhibitors exhibited significantly suppressed AKT/mTOR signaling pathway in liver, muscle, and adipose tissues, as well as downregulation of genes associated with energy and lipid metabolism (L-Fabp, Pparα/γ, Ubiad1, Cyp4a12). These findings demonstrate that inhibition of either the AKT or mTOR molecules mitigates obesity and metabolic dysregulation in Riz1-/- mice, highlighting the critical role of the RIZ1/AKT/mTOR axis in maintaining metabolic homeostasis."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • Solid Tumor • Thymoma • Thymus Cancer • FABP1 • PPARA

Expected upcoming milestones in second half of 2025 (Laekna Press Release) - "To complete subject enrollment of AFFIRM-205 Phase III China trial."

Enrollment status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

AKT inhibitors in gynecologic oncology: past, present and future. (PubMed, Front Oncol) - "Currently, multiple classes of AKT inhibitors-PH domain competitors (perifosine), allosteric inhibitors (MK-2206), and ATP-competitive agents (AZD5363, GSK2110183, GSK2141795, and GDC-0068) are under development, with several agents in phase II/III trials. This study systematically reviews recent AKTi research in gynecological cancers, aiming to provide a theoretical foundation for identifying potential biomarkers, overcoming drug resistance, and developing prognostic models. These insights may further facilitate the clinical translation of key therapeutic agents."

Journal • Review • Gynecologic Cancers • Oncology

Analysis of immune cell infiltration in the tumor microenvironment of cervical cancer and its impact on immunotherapy. (PubMed, Front Oncol) - "Drug sensitivity analysis indicated increased responsiveness of high-risk patients to agents such as Afuresertib and Venetoclax. The findings contribute to a more comprehensive understanding of the disease and provide a foundation for future clinical applications. Nevertheless, further large-scale validation is required to confirm these findings and enhance their clinical utility."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Cervical Cancer • Oncology • Solid Tumor • BIRC5 • CD34 • CXCL12 • PCNA • TMB

Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia. (PubMed, Discov Oncol) - "We revealed a positive correlation between the Nscore and macrophage M1, suggesting potential drug response mechanisms. Based on the identified AML subtypes and their distinct mutational landscapes, we predicted potential treatment options, with Paclitaxel, Afuresertib, and Mitoxantrone emerging as potential therapeutic agents for the AML subtypes."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP1 • COL2A1 • ITGB2 • NFKB2 • NLRP3 • PYCARD

CD52 PROMOTER METHYLATION PREDICTS RESPONSE TO AKT-TARGETING DRUGS IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "Sensitivity to Akt inhibitors (Uprosertib/Afuresertib) was tested in ten wild-type (WT) cell lines and SET-2 shRNA model via MTT. CD52, an indicator of poor prognosis in AML, is associated with Akt expression in cell lines and patients. This seems to contribute to an aggressive phenotype characterized by enhanced cell proliferation and viability, resulting in a reduced survival rate in AML patients. This finding underlines the potential of targeting Akt in AML depending on the CD52 methylation profile, based on the favorable results obtained in vitro."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD52

Predictive Oncology Reports First Quarter 2025 Financial Results and Provides Corporate Update (GlobeNewswire) - "Announced that, using publicly available datasets on drugs that have either been abandoned or discontinued by large pharmaceutical companies, Predictive has developed a registry of promising candidates that can potentially be repurposed for additional or alternative indications. Predictive’s initial screening approach on a small, curated cohort of abandoned drugs identified three compounds that warrant further exploration in new colon and breast tumor indications. Specifically, Afuresertib (breast), Alisertib (colon) and Entinosta (colon) demonstrated the highest proportion of hits within those two tumor types." "

Clinical • Breast Cancer • Colon Cancer • Colorectal Cancer

Prognostic and immunological role of RHEBL1 in pan-cancer: a target for survival and immunotherapy. (PubMed, Discov Oncol) - "Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib."

IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • CD8 • RHEB

CanSeer: a translational methodology for developing personalized cancer models and therapeutics. (PubMed, Sci Rep) - "To exemplify, three use cases involving paired samples, unpaired samples, and cancer samples only, of lung squamous cell carcinoma (LUSC) patients are provided. CanSeer reveals the effectiveness of repositioned drugs along with the identification of several novel LUSC treatment combinations including Afuresertib + Palbociclib, Dinaciclib + Trametinib, Afatinib + Oxaliplatin, Ulixertinib + Olaparib, etc."

Journal • Preclinical • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

An open-label randomized active-controlled phase II clinical study to assess the efficacy and safety of afuresertib plus paclitaxel versus paclitaxel in patients with platinum-resistant ovarian cancer (PROFECTA-II/GOG-3044). (PubMed, Gynecol Oncol) - P2 | "The addition of afuresertib to paclitaxel did not significantly improve PFS/OS in patients with PROC. However, exploratory biomarker findings suggest potential efficacy in phospho-AKT positive patients, warranting further investigation. The safety/tolerability profile of A + P was consistent with prior AKT-inhibitor studies."

Clinical • Journal • P2 data • Platinum resistant • Gastrointestinal Disorder • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • BRCA2 • PI3K • PROC • PTEN