VIC-1911 / Otsuka, VITRAC Therap - LARVOL DELTA

Combination AURKA and WEE1 inhibition exhibits efficacy in EGFR or pan-ERBB inhibitor resistant head and neck squamous cell carcinoma. (PubMed, Cancer Res Commun) - "To identify strategies to overcome resistance in HNSCC, we developed HNSCC cell models that were treatment-naïve parental, or selected for resistance to the EGFRi erlotinib, or the ERBBi afatinib. Based on increased AURKA dependence, we compared combination of VIC-1911 with adavosertib, an inhibitor of the cell cycle checkpoint regulator WEE1, in parental versus resistant models. These showed a combination effect both in vitro and in vivo, that was retained in ERBBi-resistant xenografts, suggesting the potential value of combined AURKA and WEE1 inhibitor use in patients with ERBB inhibitor-resistant HNSCC."

Journal • Head and Neck Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AURKA • EGFR • NEDD9

A first-in-human trial in advanced liver cancer guided by an in vivo CRISPR screen (EACR 2026) - P=N/A | "The combination of lenvatinib with AURKA inhibitors alisertib or vic-1911 exhibited robust antitumor effects across CDXs, PDOs, PDXs, immunocompetent mouse models, and 3D but not 2D culture. We identified AURKA as an in vivo-specific synthetic target of lenvatinib and combined AURKA inhibition with lenvatinib exhibited potent early clinical activity in HCC. This work provides proof-of-concept that in vivo CRISPR screen-guided target discovery can be successfully translated to early-phase clinical evaluation, establishing a promising combinatorial strategy for advanced HCC."

First-in-human • Metastases • P1 data • Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • DDR1

Lenvatinib Plus VIC-1911 in Lenvatinib-unresponsive or Lenvatinib-resistant HCC (clinicaltrials.gov) - P=N/A | N=5 | Terminated | Sponsor: RenJi Hospital | N=30 ➔ 5

Enrollment change • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Lenvatinib Plus VIC-1911 in Lenvatinib-unresponsive or Lenvatinib-resistant HCC (clinicaltrials.gov) - P=N/A | N=30 | Terminated | Sponsor: RenJi Hospital | Recruiting ➔ Terminated; The study was terminated because the originally planned VIC-1911 dose-escalation scheme (100 mg, 150 mg, 200 mg BID) was scientifically unjustified, lacking prior clinical safety data to support such starting doses when combined with lenvatinib in HC

Trial termination • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Safety and Efficacy Study of Lenvatinib Combined With VIC-1911 for the Treatment of Advanced HCC (clinicaltrials.gov) - P=N/A | N=15 | Active, not recruiting | Sponsor: RenJi Hospital | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jul 2025 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Aurora kinase A inhibition overcomes tolerance to panHER inhibitors in HPV positive HNSCC (AACR 2025) - "We demonstrate that although panHER inhibitors afatinib and dacomitinib more effectively inhibit growth of HPV+ HNSCC cells than do erlotinib or cetuximab, adaptive signaling through the AURKA/PLK1 axis mediates resistance to panHER inhibitors...Indeed, cell viability experiments and clonogenic survival assays demonstrate strong synergy between panHER and AURKA inhibitors, confirmed in xenografted tumor models treated with the second generation AURKA inhibitor VIC-1911 and dacomitinib...In contrast, addition of AURKA inhibition upregulated PLK1 and pPLK1 and cell death markers. These findings indicate that combination therapy with AURKA inhibition will mitigate the adaptability to EGFR and panHER inhibitors previously described for HPV+ HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AURKA • ERBB3 • PLK1

AURKA inhibitor VIC-1911 induces mitotic defects and functional BRCAness, sensitizing prostate cancer to PARP inhibition. (PubMed, JCI Insight) - "Mechanistically, VIC-1911 disabled HR-mediated repair of DSBs in otherwise HR-proficient PC cells, leading to a "BRCAness" phenotype and pronounced accumulation of DNA damage and mitotic catastrophe. In summary, our study uncovers what we believe a novel mechanism to functional "BRCAness" by inducing mitotic arrest and highlights VIC-1911 as a promising therapeutic agent for advanced PC, either as a single agent or in combination, sensitizing HR-proficient tumors to PARP inhibitors."

Journal • Gene Therapies • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • AURKB

Targeting Aurora Kinase A to Prevent GVHD and Relapse after Myeloablative Allogeneic Hematopoietic Cell Transplantation. (PubMed, Blood Adv) - P1/2 | "The success of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has driven efforts to optimize partner therapies that balance GVHD and relapse prevention. We report phase I dose-finding results of PTCy, sirolimus (SIR), and VIC-1911, a selective oral Aurora kinase A (AURKA) inhibitor, following myeloablative allogeneic hematopoietic cell transplantation (alloHCT)...Clinical outcomes included no grade III-IV acute GVHD through day 180 (0%) and low rates of moderate/severe chronic GVHD (6%) and relapse (0%) through 1 year (5/16 received maintenance). The 1-year overall survival for this cohort was 94%.VIC-1911 at 75 mg BID, combined with PTCy and SIR, effectively suppresses AURKA activity, offering promising GVHD and relapse prevention with a favorable safety profile and promising early clinical outcomes."

Journal • Acute Graft versus Host Disease • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • AURKA • CD4

GVHD: A Preliminary Clinical Study on the Efficacy of Cyclophosphamide and Sirolimus Combined With VIC-1911 in Preventing Graft-versus-Host Disease After Haploidentical Stem Cell Transplantation in Children (clinicaltrials.gov) - P1 | N=9 | Not yet recruiting | Sponsor: Shanghai Jiao Tong University School of Medicine

New P1 trial • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation • TP53

NN-01-195, a novel conjugate of HSP90 and AURKA inhibitors, effectively targets solid tumors. (PubMed, Mol Cancer Ther) - "We developed NN-01-195 as a novel chimeric small molecule that combines an AURKA inhibitor related to TAS-119/VIC-1911 with an HSP90-binding moiety related to SNX2112, and evaluated its function. Further, in combination with an inhibitor of the G2/M checkpoint protein WEE1, NN-01-195 is more potent than VIC-1911 in limiting growth of xenograft tumors. These data support the exploration of NN-01-195 and improved analogs as promising new candidates for therapeutic evaluation."

Journal • Oncology • Solid Tumor • CDC37 • HSP90AA1

PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation (clinicaltrials.gov) - P1/2 | N=16 | Completed | Sponsor: Masonic Cancer Center, University of Minnesota | Active, not recruiting ➔ Completed | Trial completion date: Mar 2028 ➔ Jun 2025

Trial completion • Trial completion date • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation

Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus (ASH 2023) - P1/2 | "Introduction: With the wider use of post-transplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis, there is interest in replacing tacrolimus (TAC) with sirolimus (SIR, mTOR inhibitor) to avoid calcineurin inhibitor toxicity, maintain excellent GVHD control, and potentially allow for a greater graft-versus-tumor effect...Patients undergoing myeloablative TBI-based alloHCT with PTCy/SIR plus mycophenolate mofetil (MMF), without VIC on a separate protocol, served as a control...Unlike alisertib, VIC-1911 is not myelosuppressive, providing rationale for this trial... A VIC-1911 dose of 75 mg BID from day +5 to day +45 effectively suppresses AURKA activity as determined by a low frequency of pH3ser10+ CD4+ T cells, ablating CD28 T cell costimulation when combined with sirolimus, resulting in no dose-limiting toxicities. VIC 75 mg BID will be studied further in an expanded phase I cohort to obtain estimates of efficacy in preventing both GVHD and..."

Combination therapy • P1 data • Acute Respiratory Distress Syndrome • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • AURKA • CD4

VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Vitrac Therapeutics, LLC | Phase classification: P1a/1b ➔ P1

Monotherapy • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Dual targeting of Aurora Kinase A and poly (ADP-ribose) polymerase as a therapeutic option for patients with ovarian cancer: preclinical evaluations. (PubMed, J Cancer Res Clin Oncol) - "Our studies indicate a synergistic benefit from combined PARPi and AURKAi in mutant and wild-type BRCA EOC tumors."

Journal • Preclinical • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • AURKA • BRCA • BRCA1 • BRCA2 • PARP1

PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: Masonic Cancer Center, University of Minnesota | Recruiting ➔ Active, not recruiting | N=75 ➔ 16 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Enrollment change • Enrollment closed • Trial primary completion date • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leukemia • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • Transplantation • CD4

Safety and Efficacy Study of Lenvatinib Combined With VIC-1911 for the Treatment of Advanced HCC (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: RenJi Hospital

Metastases • New trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Phase I trial of aurora kinase A (AURKA) inhibitor VIC-1911 plus osimertinib for TKI-resistant, EGFR-mutant non-small cell lung cancer (NSCLC). (ASCO 2024) - P1 | "VIC-1911 in combination of osimertinib is well-tolerated in previously-treated EGFRmt NSCLC. The combination demonstrates sustained antitumor activity, which indicates the potential of AURKA blockade in delaying the emergence of resistance to osimertinib."

P1 data • Hematological Disorders • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • AURKA • EGFR

Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus (TCT-ASTCT-CIBMTR 2024) - P1/2 | "Introduction: The rising use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has sparked interest in finding better drug partners to achieve efficient GVHD control while enhancing graft-versus-tumor effects...Patients receiving PTCy/SIR/mycophenolate mofetil (MMF) in a separate clinical trial serve as controls for studies of CD4+ immunophenotyping. Prior experiments combining PTCy/SIR with another AURKA inhibitor, alisertib, showed significant protection against GVHD and tumor recurrence in mice (Figure 1A-C)... VIC-1911 (75 mg BID) effectively suppresses AURKA activity when combined with SIR, showing no dose-limiting side effects. The ongoing phase I expansion study will further assess VIC-1911's potential in preventing GVHD and relapse in PTCy-based alloHCT."

Combination therapy • P1 data • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • AURKA • CD4

Selective Oral AURKA Inhibitor Treatment for Graft-Versus-Host Disease and Relapse Prophylaxis Following Allogeneic HCT: Single-arm Phase 1 Dose Escalation Trial (HMP Global) - "At the 65th American Society of Hematology (ASH) Annual Meeting, Shernan G Holtan, MD...discusses a phase 1 dose escalation portion of a first-in-human clinical trial of post-transplant cyclophosphamide (PTCy) plus sirolimus and selective oral AURKA inhibitor VIC-1911 for graft-versus-host disease (GVHD) and relapse prophylaxis after myeloablative allogeneic hematopoietic cell transplantation (alloHCT)."

Video

Lenvatinib Plus VIC-1911 in Lenvatinib-unresponsive or Lenvatinib-resistant HCC (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: RenJi Hospital | Not yet recruiting ➔ Recruiting | Initiation date: Feb 2023 ➔ Jul 2023

Enrollment open • Trial initiation date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

Against HER2-negative breast cancer! The combination of Aurora A inhibitor was declared for clinical trial (163.com) - "...Genesis announced that the Investigational New Drug (IND) application for its innovative small molecule Aurora A inhibitor VIC-1911 in combination with the PARP inhibitor olaparib for the treatment of advanced breast cancer has been accepted by the National Medical Products Administration (NMPA) of China. The Phase 1/2 study is designed to evaluate the safety, tolerability, pharmacokinetic profile and preliminary efficacy of VIC-1911 tablets as a single agent or in combination with olaparib in patients with advanced solid tumors and in combination with advanced HER2-negative breast cancer."

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

VIC-1911 With/Without Sotorasib Under Investigation in KRAS G12C Inhibitor–Resistant and –Naïve NSCLC (OncLive) - P1 | N=NA | NCT05374538 | Sponsor: Vitrac Therapeutics, LLC | Sarah Goldberg, MD, MPH, expanded on the details of this ongoing study at the 2023 ASCO Annual Meeting. In the nonrandomized, open label, dose-escalation phase of the study, patients will be assigned to cohort 1a or cohort 1b. Cohort 1a consists of patients with relapsed/refractory disease who will receive VIC-1911 monotherapy. Cohort 1b is comprised of patients with relapsed/refractory disease who were previously treated with a KRAS G12C inhibitor, or patients who are naïve to prior KRAS G12C inhibitor therapy. Patients in this cohort will be treated with VIC-1911 plus sotorasib....The preclinical data that led to the rationale for this study [were generated] in part by Barbara Burtness, MD...found that the combination of VIC-1911 and sotorasib appeared to be effective in cell and animal models of KRAS G12C–mutant NSCLC."

P1 data

SYNERGISTIC TARGETING OF KIF11 AND AURKA TO IMPROVE OUTCOMES FOR EWING SARCOMA (CTOS 2023) - "Given the lack of clinical grade KIF15 inhibitors, we targeted the protein upstream by inhibiting AURKA (VIC-1911; VITRAC Therapeutics) to block phosphorylation of KIF15S1169 and its subsequent targeting to the spindle... We have identified a novel combination of mitotic inhibitors targeting KIF11 and KIF15 via AURKA that is highly synergistic in inhibiting the growth of an aggressive tumor such as Ewing sarcoma. Our findings are highly relevant, timely and clinically translatable given the lack of proper therapies for this rare and orphaned disease"

Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • AURKA • EWSR1 • FLI1 • KIF11 • KIF15 • PARP1

VIC-1911 With/Without Sotorasib Under Investigation in KRAS G12C Inhibitor–Resistant and –Naïve NSCLC (OncLive) - "In the nonrandomized, open label, dose-escalation phase of the study, patients will be assigned to cohort 1a or cohort 1b. Cohort 1a consists of patients with relapsed/refractory disease who will receive VIC-1911 monotherapy. Cohort 1b is comprised of patients with relapsed/refractory disease who were previously treated with a KRAS G12C inhibitor, or patients who are naïve to prior KRAS G12C inhibitor therapy. Patients in this cohort will be treated with VIC-1911 plus sotorasib....In the dose expansion phase, patients will be enrolled onto cohorts 2a, 2b, or 2c. Cohort 2a will include patients with relapsed/refractory disease who will receive VIC-1911 monotherapy. Patients in cohort 2b with relapsed/refractory disease who received a prior KRAS G12C inhibitor will be treated with the combination of VIC-1911 and sotorasib. Lastly, patients naïve to a KRAS G12C inhibitor in cohort 2c will be treated with the combination regimen."

Clinical protocol • Non Small Cell Lung Cancer

Inducing Mitotic Catastrophe as a Therapeutic Approach to Improve Outcomes in Ewing Sarcoma. (PubMed, Cancers (Basel)) - "In vivo studies in EWS xenograft mouse models showed significant tumor reduction and overall effectiveness: drug combination vs. vehicle control (p ≤ 0.01), SB-743921 (p ≤ 0.01) and VIC-1911 (p ≤ 0.05). Kaplan-Meier curves demonstrated superior overall survival with the combination compared to vehicle or monotherapy arms (p ≤ 0.0001)."

Journal • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • AURKA • EWSR1 • FLI1 • KIF11 • KIF15 • KIF5B