VIC-1911

P1, N=3, Terminated, Vitrac Therapeutics, LLC | Phase classification: P1a/1b --> P1

Our studies indicate a synergistic benefit from combined PARPi and AURKAi in mutant and wild-type BRCA EOC tumors.

P1/2, N=16, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=75 --> 16 | Trial primary completion date: Mar 2025 --> Sep 2024

P=N/A, N=15, Recruiting, RenJi Hospital

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.