However, overexpression of ABCG2 failed to confer resistance to 2257 in TNBC xenografts grown in mice and treated with a moderately active dose and schedule. Our results highlight the potential impact of drug transporters in in vitro CRISPR screens and the importance of confirming the relevance of drug response mechanisms identified in cultured cells using in vivo models that recapitulate drug pharmacokinetics and pharmacodynamics.

P1/2, N=37, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2025 --> Dec 2026

P1, N=260, Recruiting, SillaJen, Inc. | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Dec 2026

Here, we extended those studies into syngeneic murine models of TNBC using two TTK inhibitors: empesertib and the novel TTK inhibitor CFI-402257 (also known as luvixasertib) that was recently granted FDA fast track approval in breast cancer. Taken together, these studies demonstrate that TTK inhibition enhances radiosensitivity and TTK inhibition with RT modulates the immune landscape of TNBC. Collectively, this combination may represent a novel therapeutic strategy to improve outcomes for patients with TNBC by both direct tumor cytotoxicity and by promoting an immune-responsive environment.

P1/2, N=44, Active, not recruiting, Treadwell Therapeutics, Inc | Recruiting --> Active, not recruiting | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P1/2, N=31, Terminated, Nerviano Medical Sciences | Completed --> Terminated; In the Phase II part of the study, among the participants evaluable for efficacy, no objective (partial response or clinical response) was observed at the first futility analysis.

P1/2, N=37, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2024 --> Dec 2025

CFI-402257, a specific inhibitor of TTK, is found to exhibit anti-tumor effects and exerted synergistic efficacy with PI3K inhibitor, Duvelisib, in TCL. The study shows that TTK contributes to the development of TCL by regulating p38α-mediated AMPK/mTOR pathway. CFI-402257 is expected to be a promising strategy for TCL treatment.

The TP53MUT-resistant line can tolerate aneuploidy or polyploidy and exhibits drug resistance. Our study explores the potential of an MPS1/TTK inhibitor, compound-9, as a targeted therapy in gastric cancer cells and investigates its mechanism of action.

Furthermore, MPH-5 showed potent inhibition of HepG2 xenograft tumor growth in mice with no apparent toxicity and presented favorable pharmacokinetics. The study suggests that MPH-5 is a potent, selective, high-efficacy, and low-toxicity antitumor candidate for the treatment of hepatocellular carcinoma.

P1/2, N=31, Completed, Nerviano Medical Sciences | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Aug 2024

P1, N=216, Recruiting, SillaJen, Inc. | N=120 --> 216