VIC-1911

P=N/A, N=30, Recruiting, RenJi Hospital | Not yet recruiting --> Recruiting | Initiation date: Feb 2023 --> Jul 2023

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 relapse in PTCy-based myeloablative alloHCT.

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).

P1a/1b, N=4, Terminated, 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

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

P1, N=72, Recruiting, Jiesi Yingda Pharmaceutical Technology (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

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.

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.

JSI-1187 or VIC-1911 combined with sotorasib or adagrasib demonstrated marked enhancement of the antitumor effect compared with single-agent treatment in a H2122 mouse xenograft model. Additionally, the antitumor growth effect of JSI-1187 and sotorasib was significantly better than the combination of the MEK inhibitor, trametinib, and sotorasib...In addition, the combination of JSI-1187 and sotorasib demonstrated a significant increase in tumor growth inhibition in a CRC PDX model. Taken together, our preclinical studies suggest that the combination of an ERK inhibitor, JSI-1187, or an AURKA inhibitor, VIC-1911, may potentially overcome the primary resistance and prevent or delay the acquired resistance to G12C inhibitors.

Using viability and clonogenic assays, we have found that the AURKA inhibitor VIC-1911 synergizes with the EGFR inhibitors afatinib and erlotinib in multiple HNSCC cell lines and retains activity in HNSCC cell models selected for resistance to these EGFR inhibitors. Dual inhibition of AURKA in combination with inhibitors of glycolytic enzymes, or enzymes regulating oxidative phosphorylation, showed marked synergy. These and other results investigating AURKA signaling mechanisms in HNSCC demonstrate that the non-canonical functions of AURKA include viable therapeutic targets that can enhance the efficacy of AURKA inhibition in HNSCC.

P1a/1b, N=140, Recruiting, Vitrac Therapeutics, LLC | Not yet recruiting --> Recruiting | Phase classification: P1 --> P1a/1b | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: May 2025 --> Mar 2026

P1, N=140, Not yet recruiting, Vitrac Therapeutics, LLC | Initiation date: Jun 2022 --> Sep 2022

P1, N=140, Not yet recruiting, Vitrac Therapeutics, LLC

P1/2, N=75, Recruiting, Masonic Cancer Center, University of Minnesota | Not yet recruiting --> Recruiting

P1/2, N=75, Not yet recruiting, Masonic Cancer Center, University of Minnesota

No abstract available

TAS-119 inhibited TRK-fusion protein activity and exhibited robust growth inhibition of tumor cells via a deregulated TRK pathway in vitro and in vivo. Our study indicates the potential of TAS-119 as an anticancer drug, especially for patients harboring MYC amplification, CTNNB1 mutation, and NTRK fusion.

TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors.