LY3295668 / Eli Lilly - LARVOL DELTA

A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma (clinicaltrials.gov) - P1 | N=71 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Neuroblastoma • Oncology • Solid Tumor

Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for the Treatment of Advanced or Metastatic EGFR-Mutant Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase 1 dose-escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma. (PubMed, Cancer) - "LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof-of-concept clinical responses were observed, future studies with biomarker-selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition."

Journal • Monotherapy • P1 data • CNS Tumor • Hematological Disorders • Mucositis • Neuroblastoma • Neutropenia • Oncology • Solid Tumor • AURKA

Deciphering the Glycosylation Status of Programmed Cell Death Ligand 1 and its regulation by Aurora Kinase A in Hepatocellular Carcinoma (LCS 2025) - "Treatment with MG-132 markedly increase PD-L1, indicating its susceptibility to proteasomal degradation. Inhibition of AURKA using AK-01 significantly downregulated PD-L1 expression, particularly in the mature forms, whereas si-AURKA took 144 hours to achieve a comparable level of downregulation... The differing glycosylation patterns between JHH6 and HuH7 cells may reflect the heterogeneous glycosylation in HCC. Additional HCC models are essential to uncover potentially distinct PD-L1 half-life profiles. Understanding PD-L1 stability and degradation mechanisms in HCC provides valuable insights into PD-L1 functionality, supporting more targeted treatment strategies."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AURKA • PD-L1

A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma (clinicaltrials.gov) - P1 | N=71 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2024 ➔ Aug 2025

Trial completion date • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Microchip isotachophoresis for green and sustainable pharmaceutical quality control: Method validation and application to complex pharmaceutical formulations. (PubMed, J Chromatogr A) - "Universal microchip isotachophoresis (μITP) methods were developed for the determination of cationic and anionic macrocomponents (active pharmaceutical ingredients and counterions) in cardiovascular drugs marketed in salt form, amlodipine besylate and perindopril erbumine...The developed methods allowed precise and accurate determination of the studied analytes, the RSD of the quantitative and qualitative parameters were less than 1.5% and the recoveries ranged from 98 to 102%. The developed μITP methods were successfully applied to the determination of cationic and anionic macrocomponents in six commercially available pharmaceutical formulations."

Journal • Cardiovascular

Aurora kinase A and programmed death-ligand 1: expression dynamics in hepatocellular carcinoma development and the regulatory role of the kinase in immune checkpoint modulation (EASL-ILC 2024) - "AURKA was inhibited by alisertib or AK-01 for 72h, and knockdown was achieved through siRNA for 72h or 144h in HCC-derived JHH6 and Huh7 cell lines. AURKA and PD-L1 expression positively correlate in liver disease, both increasing with the progression of the disease. AURKA exhibits higher kinase activity in tumors than in NT tissues. In vitro, AURKA inhibition or silencing decreases PD-L1 expression through two mechanisms, implying multiple roles of AURKA in the regulation of PD-L1."

IO biomarker • Breast Cancer • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • AURKA • PD-L1

FAN Trial: A randomised controlled open label trial assessing the effect of perindopril erbumine on Fontan-Associated Nephropathy (ANZCTR) - P4 | N=50 | Not yet recruiting | Sponsor: Australian Heart Foundation

New P4 trial • Cardiovascular • Heart Failure • Renal Disease • CST3

Combination of an aurora kinase inhibitor and the ABL tyrosine kinase inhibitor asciminib against ABL inhibitor-resistant CML cells. (PubMed, Med Oncol) - "It also evaluated the efficacy of the ABL TKI asciminib and the aurora kinase inhibitor LY3295668. Combining asciminib and aurora kinase inhibition enhanced the efficacy and is proposed as a new therapeutic option for patients with CML. These findings have clinical implications for a potential novel therapeutic strategy for CML patients."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • AURKA • AURKB

AURKA‐inhibitor resistant CAR T cells in combination with AURKAi for advanced neuroblastoma cell killing (ESGCT 2023) - "Thus, Aurora A kinase inhibitors (AURKAi), such as the highly effective AURKAi LY3295668, are becoming interesting candidates to indirectly inhibit MYCN activity by causing its proteasomal degradation...CAR T cell function is assessed by their release of effector cytokines (IFNG and IL2), expression of markers of activation (CD69, CD25, CD137) and exhaustion (LAG3, TIM3, PD-1) and their cytotoxic potential using the Incucyte live cell analysis instrument to detect tumor cell killing. The data will show whether the combination of neuroblastoma-specific CAR T cells equipped with AURKA T217A mutant and pharmacological inhibition of MYCN can enhance killing efficacy against MYCN-amplified neuroblastoma cell lines and improve therapeutic outcome for patients in the clinic."

CAR T-Cell Therapy • Combination therapy • IO biomarker • Metastases • CNS Tumor • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • AURKA • CD69 • HAVCR2 • IFNG • IL2 • IL2RA • L1CAM • LAG3 • MYCN • TNFRSF9

AB-218-IIT-201: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Melbourne Health | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

A phase Ib/II trial to evaluate safety and efficacy of aurora kinase inhibitor LY3295668 in combination with osimertinib for patients with EGFR-mutant non-small cell lung cancer (ELCC 2024) - P1/2 | "Conclusions The combination of LY3295668 25mg BID plus osimertinib 80mg daily was found to be safe in EGFR-mutant NSCLC pts. The combination yields a 6-month PFS rate of 37% with 11% PR and 63% SD, demonstrating moderate clinical efficacy."

Clinical • Combination therapy • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • EGFR

Structure-Guided Optimization of InSTIs to Increase Antiviral Potencies Against HIV-1 IN Mutants (CROI 2024) - "Although AK-01 is not a fully optimized compound, our results show that combining structural modifications of promising naphthyridine-based INSTIs can be used to produce new compounds that are effective against some of the known drug-resistant mutants. Importantly, AK-01 had an improved antiviral profile when compared to cabotegravir. We are currently using the available structural and virological data to design and evaluate additional INSTIs."

Human Immunodeficiency Virus • Infectious Disease

A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma (clinicaltrials.gov) - P1 | N=71 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2023 ➔ Aug 2024

Trial completion date • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor

Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for the Treatment of Advanced or Metastatic EGFR-Mutant Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2024 ➔ Jun 2025 | Trial primary completion date: May 2024 ➔ Jun 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bioequivalence Study of Perindopril /Amlodipine/Indapamide 8 mg (10 mg)/2.5 mg/10 mg Tablets in Healthy Volunteers Under Fasting Conditions (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Pharmtechnology LLC

New P1 trial

Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for the Treatment of Advanced or Metastatic EGFR-Mutant Non-squamous Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safusidenib Phase 2 Study in IDH1 Mutant Glioma (clinicaltrials.gov) - P2 | N=95 | Recruiting | Sponsor: AnHeart Therapeutics Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Feb 2027 ➔ Jul 2027 | Trial primary completion date: Jan 2026 ➔ Mar 2027

Enrollment open • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1

The role of Aurora kinase A in hepatocellular carcinoma: possible regulation of Programmed death-ligand 1 (LCS 2023) - "JHH6 cells, an undifferentiated HCC-derived in vitro model, were treated for 72 hours with two inhibitors of the kinase activity of AURKA (Alisertib and AK-01) and short interfering RNA (siRNA) targeting AURKA. AURKA is positively correlated with PD-L1 in both HCC and non-tumor tissues. The inhibition of kinase activity of AURKA enhances the number of polynucleated cells due to defects in chromosome separation and incorrect mitosis. The reduced expression of PD-L1 following AURKA inhibition highlights the potentiality of AURKA inhibitors in cancer therapy, possibly in combination with new immune checkpoint inhibitors."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AURKA • LATS2 • PD-L1

Population pharmacokinetics of an aurora kinase A inhibitor, LY3295668 erbumine (AK-01), in patients with locally advanced or metastatic solid tumors (AACR 2019) - P1/2; "At the MTD of 25 mg BID, steady state LY3295668 plasma concentrations are maintained above the pAurA IC90 for the entire dosing interval, exceeding the minimum requirements for efficacy associated with non-clinical xenograft models. Trial Registration: NCT03092934"

Clinical • PK/PD data

KEYNOTE E27: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) (clinicaltrials.gov) - P1a/1b | N=400 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Nov 2023 ➔ Sep 2025 | Trial primary completion date: Nov 2023 ➔ Sep 2025

Metastases • Trial completion date • Trial primary completion date • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • KRAS • PD-L1

Exploration of Polymethacrylate and Hypromellose for the development of a non-sulfhydryl ACE inhibitor mucoadhesive system using Box-Behnken Design: In-vitro and Ex-vivo evaluation. (PubMed, Drug Dev Ind Pharm) - "The lag time for coated tablet P1T3 came to 2.15 ± 0.15 h and for P2T8 11.9 ± 0.10 h proving the coating efficiency of polymers. The current study strongly suggests that perindopril Erbumine in association with Eudragit and Hypromellose polymer can open a path for the time-regulated release of the drug for hypertension chronotherapy with less risk of dose dumping."

Journal • Preclinical • Cardiovascular • Hypertension

A first-in-human phase 1 study of LY3537982, a novel, highly selective and potent KRAS G12C inhibitor in patients with KRAS G12C mutant advanced solid tumors (trial in progress) (AACR 2022) - P1a/1b | "Key objectives of Phase 1b are to determine the safety and tolerability of LY3537982 monotherapy, and in combination with various agents: abemaciclib, erlotinib, cetuximab, an investigational ERK inhibitor (LY3214996), an investigational Aurora A kinase inhibitor (LY3295668), and an anti-PD1 antibody. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS malignancy, symptomatic CNS metastasis, or carcinomatous meningitis. The trial is currently enrolling patients (NCT04956640)."

Clinical • IO biomarker • P1 data • Brain Cancer • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • KRAS

EXPLORING THE EFFECTS OF AURORA KINASE A INHIBITION IN LIVER CANCER: A POSSIBLE LINK TO PD-L1 REGULATION (ILCA 2022) - "This study aims to evaluate the effects of two different AURKA inhibitors (Alisertib and AK-01) in liver cancer, focusing on the role of AURKA in the regulation of Programmed deathligand 1 (PD-L1) expression. This study underlines the relevance of AURKA as a key player in liver cancer thus suggesting possible future applications of AURKA inhibitors as therapy for liver cancer. In this regard, the link with PD-L1 may suggest a feasible strategy consisting of the use of AURKA inhibitors in combination with PD-1/PD-L1 inhibitors."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKA

A Study of LY3295668 Erbumine in Participants With Relapsed/Refractory Neuroblastoma (clinicaltrials.gov) - P1 | N=71 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Aug 2022 ➔ Aug 2023

Trial completion date • Neuroblastoma • Oncology • Solid Tumor