Biosplice Therapeutics said the first patient has been dosed in an open-label, investigator-initiated Phase 1 clinical trial evaluating cirtuvivint in combination with the PARP inhibitor olaparib for women with BRCA-mutated and/or homologous recombination-deficient (HRD) platinum-resistant ovarian cancer. The study is being conducted at University of Colorado Anschutz Cancer Center and sponsored by UCHealth University of Colorado Hospital.
The trial, titled “Cirtuvivint and Olaparib for the Treatment of Patients with BRCA/HRD Platinum Resistant Ovarian Cancer”, uses a dose-escalation design followed by a dose-expansion cohort to assess the safety, tolerability and recommended Phase 2 regimen of the combination in patients who have previously received PARP inhibitor therapy. Cirtuvivint is a small-molecule inhibitor of CDC-like kinases (CLK) and DYRK kinases designed to modulate alternative RNA splicing and disrupt pathways that contribute to cancer cell survival and drug resistance.
Preclinical data from collaborators at Colorado Anschutz suggest that combining cirtuvivint with olaparib may overcome or delay resistance to PARP inhibition—a common clinical challenge in high-grade serous ovarian cancer—by indirectly suppressing WNT/TCF signaling, inducing DNA damage and enhancing anti-tumor effects in laboratory models. Both agents are fully oral, potentially offering accessible treatment for patients with limited options.
The Phase 1 trial aims to identify a safe and tolerable dose for future studies. It represents one of the first clinical efforts to combine a CLK/DYRK inhibitor with PARP inhibitor therapy in this hard-to-treat patient population, highlighting a strategy to target both DNA repair mechanisms and adaptive survival pathways in ovarian cancer.
