VIC-1911 / Otsuka, VITRAC Therap - LARVOL DELTA

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

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

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)."

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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

VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1a/1b | N=4 | Terminated | Sponsor: Vitrac Therapeutics, LLC | N=140 ➔ 4 | Trial completion date: Nov 2026 ➔ Aug 2023 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Aug 2023; Sponsor decision

Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

VIC-1911, a selective Aurora kinase A inhibitor, synergizes with sacituzumab govitecan in triplenegative breast cancer. (AACR-NCI-EORTC 2023) - No abstract available

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA

VIC-1911 Combined With Osimertinib for EGFR -Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Jiesi Yingda Pharmaceutical Technology (Suzhou) Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

VITRAC Therapeutics to Present Phase 1 Clinical Trial Design on Novel Aurora Kinase A Inhibitor, VIC-1911, and G12C Inhibitor, Sotorasib, for KRAS G12C-Mutant Non-Small Cell Lung Cancer at the 2023 ASCO Annual Meeting (Businesswire) - "'We now have two approved KRAS G12C inhibitors, sotorasib and adagrasib, to treat patients with KRAS G12C-mutated NSCLC,' stated Sarah Goldberg, MD... 'Despite the satisfactory response rates in patients naïve to KRAS G12C inhibitor therapy, over 50% of patients exhibit primary resistance. Moreover, many patients who do respond soon develop acquired resistance and relapse. With this innovative approach combining AURKA and KRAS G12C inhibitors, we aim to enhance therapeutic outcomes for our patients with KRAS G12C-mutant NSCLC.'"

Media quote • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A phase 1a/1b study of aurora kinase A inhibitor VIC-1911 as monotherapy and in combination with sotorasib for the treatment of KRAS G12C-mutant non–small-cell lung cancer. (ASCO 2023) - P1a/1b | "In addition, in vivo data suggest both sotorasib and adagrasib are synergistic in combination with VIC-1911 in human KRASG12C-mutant NSCLC cell line xenograft models. Pharmacodynamics will be determined from ctDNA and tumor biomarker analysis. Clinical trial information: NCT05374538."

Combination therapy • IO biomarker • Monotherapy • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AURKA • KRAS

VITRAC Therapeutics to Present Phase 1 Clinical Trial Design on Novel Aurora Kinase A Inhibitor, VIC-1911, and G12C Inhibitor, Sotorasib, for KRAS G12C-Mutant Non-Small Cell Lung Cancer at the 2023 ASCO Annual Meeting (Businesswire) - "VITRAC Therapeutics, LLC (VITRAC) presented a poster on the Phase 1a/1b clinical trial of aurora kinase A (AURKA) inhibitor, VIC-1911, as monotherapy and in combination with KRAS G12C inhibitor, sotorasib. The study targets the treatment of KRAS G12C-mutant non-small cell lung cancer (NSCLC). The findings were presented at the prestigious 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 4."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Dr Burtness on the Exploration of VIC1911 and Adavosertib in HNSCC and Lung Cancer (OncLive) - "Previous research has shown that Aurora kinase A (AURKA) is overexpressed in cells that have a mutational loss of TP53 function, making AURKA a promising therapeutic target, Burtness begins. In a preclinical study presented at the 2023 AACR Annual Meeting, the AURKA inhibitor, VIC1911 was combined with the WEE1 inhibitor adavosertib. Altough VIC1911 does not have some of the toxicities of prior AURKA inhibitors, this treatment is not cytotoxic because it leads to the cell going into cell cycle arrest, Burtness says."

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Dr Burtness on the Exploration of VIC1911 and Adavosertib in HNSCC and Lung Cancer (OncLive) - "In a preclinical study presented at the 2023 AACR Annual Meeting, the AURKA inhibitor, VIC1911 was combined with the WEE1 inhibitor adavosertib....Data showed that in cell line–derived xenografts and patient-derived xenografts, VIC1911 decreased DNA replication fork progression, phosphorylation of replication protein A was upregulated, and DNA damage was upregulated, Burtness says. The addition of Adavosertib amplified those effects, she says, adding that almost no normal mitotic figures that can form with this combination."

Preclinical • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Targeting of KIF11 and AURKA to improve outcomes in Ewing sarcoma (AACR 2023) - "The combination arm showed significant survival versus control (p≤ 0.001, HR=0.42, 95% CI=0.14-1.25), VIC-1911 (p≤ 0.001, HR=0.48, 95% CI=0.16-1.42) or SB-743921 (p ≤ 0.01, p≤ HR=0.71, 95% CI=0.21-2.34) alone. Efforts are underway to translate these preclinical studies into an early phase clinical trial of patients with histologically proven EWS who have failed standard of care therapy."

Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • AURKA • EWSR1 • FLI1 • KIF11

Concomitant inhibition of Aurora kinase A and WEE1 kinases results in synergistic tumor control and heightens DNA replication stress in head and neck and lung carcinomas. (AACR 2023) - "VIC1911 and adavosertib combination synergistically suppressed cell growth and survival in both 2D- and 3D-culture systems relative to vehicle or single-agent treatment in TP53-mutated HNSCC FaDu and CAL27, and lung cancer A549 and NCI-H358 cells, with no observable toxicity in normal cells, predicting a favorable therapeutic index. In vivo, this combination resulted in significant tumor regression in both HNSCC and lung adenocarcinoma patient-derived and cancer cell-derived xenografted mice compared with either vehicle or single-agent treatment. Taken together, these results suggest that AURKA inhibition increases dependency on WEE1 by enhancing replication stress and mitotic catastrophe, and support clinical evaluation of combined AURKA and WEE1 inhibition as a novel and effective treatment for HNSCC and lung cancer patients with elevated AURKA expression."

Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • AURKA • CDKN2A • TP53