"Validation of ADC Combination Efficacy Begins"... Qurient Launches Clinical Trial of Mocaciclib and Trodelvy Combination

On July 29, Qurient announced that its clinical trial plan (IND) for the combination of Mocaciclib (Q901) and TROP2-targeted antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan) has been approved by the Ministry of Food and Drug Safety (MFDS).

This clinical trial is a multi-center, investigator-initiated study led by Yonsei University Severance Hospital, aiming to evaluate the safety and efficacy of the combination therapy of Mocaciclib and Trodelvy in patients with triple-negative breast cancer (TNBC). Notably, the trial is significant as it is the first clinical study to combine Mocaciclib and a TOP1 (topoisomerase I) inhibitor payload ADC, a combination that demonstrated strong synergy in preclinical efficacy evaluations.

ADC is currently the fastest-growing modality (therapeutic approach) in the anticancer drug market. Major global pharmaceutical companies are adopting the securing of combination drugs as a key strategy to expand the therapeutic range of approved ADCs and overcome resistance. Triple-negative breast cancer is a representative refractory subtype with limited treatment options because it lacks expression of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2), which are typical targets of breast cancer treatment agents. Trodelvy is used as the standard of care for such metastatic TNBC, and this combination clinical trial will evaluate whether combining Mocaciclib can further enhance Trodelvy’s therapeutic effect and expand its indications.

In preclinical mechanism of action studies, Mocaciclib demonstrated strong efficacy as a targeted anticancer agent that selectively inhibits CDK7. By regulating transcription, Mocaciclib effectively suppressed the overactivation of the MYC transcription factor—which is frequently observed in TNBC—across various TNBC models. In addition, Mocaciclib exhibited synergy with TOP1 inhibitor ADCs that induce DNA damage, by inhibiting genes in the DNA damage repair (DDR) pathway. This allows for targeting cancer through two distinct combination mechanisms.

At the American Society of Clinical Oncology (ASCO) annual meeting this year, results from the ASCENT-03 and ASCENT-04 clinical trials for Trodelvy as a first-line therapy showed that progression-free survival improved when DNA homologous recombination repair mutations were present. This provides a rationale for combining Trodelvy with Mocaciclib, which induces homologous recombination repair deficiency.

Nam Kiyeon, CEO of Qurient, stated, “The combination of a CDK7 inhibitor and a TOP1 inhibitor-based ADC is already a powerful approach with robust preclinical evidence, and this clinical trial marks the first time this will be confirmed in humans. We hope that Mocaciclib will provide a new alternative for patients with triple-negative breast cancer, where unmet medical needs remain considerable.”

This content was produced with the assistance of AI translation services.