Exploration of PLK1 Inhibition in Advanced Cancers Begins


The investigational PLK1 inhibitor, CYC140, is the focus of important clinical research in advanced solid tumors, leukemias, and lymphomas.

cancer cell | Image Credit: © vitanovski - www.stock.adobe.com

Image Credit: © vitanovski - www.stock.adobe.com

Studies are underway to assess the use of the novel PLK1 inhibitor, CYC140, for the treatment of patients with various advanced tumors, including advanced lymphoma, leukemia, and myelodysplastic syndrome (MDS).1-2

Preclinically, CYC140 demonstrated encouraging antitumor activity and antiproliferative activity in multiple tumor types, including esophageal cancer and acute leukemia xenograft models. The activity shown was consistent with the known apoptotic mechanism of PLK1 inhibitors.3

Based on the preclinical data, researchers suggested that CYC140 could be added to various combination regimens showing promise in advanced cancers.

To date, a first-in-human protocol, and a phase 1/2 study have been initiated.1

Phase 1 Study

The first-in-human, open-label, single-arm, dose-escalation study of CYC140 (NCT03884829) has begun at the University of Texas MD Anderson Cancer Center. The study is intended for patients with advanced acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, and MDS. The overarching goal of the study is to examine the pharmacokinetics of CYC140 in these patient populations.

The primary end point of the study is the number of patients who experience dose-limiting toxicities (DLT), and the secondary end point is plasma drug exposure area under the curve. Another outcome being explored in the study is antitumor activity determined by the rate of complete remissions and partial remissions.

Patients eligible to enroll in the study are those with a diagnosis of relapsed or refractory leukemia or MDS, an ECOG performance score of 0-2, and adequate renal and liver function. Patients are required to be ≥ 2 weeks from prior chemotherapy, radiation therapy or major surgery, and ≥ 4 weeks from other investigational anticancer therapy. All patients are also required to use contraception during the study.

The phase 1 study excludes patients with known central nervous system involvement, uncontrolled intercurrent illness, known human immunodeficiency virus, and active hepatitis B and/or hepatitis C infection. Patients who are receiving radiotherapy, biological therapy, or any other investigational agents are also excluded from the study, along with patients who are pregnant or lactating.

Once enrolled, patients will be dosed with single-agent CYC140 on day 1 and day 8 of each 3-week cycle. Approximately 50 patients with advanced leukemia and MDS are being actively recruited for the study.

Phase 1/2 Study

CYC140 is also being investigated in phase 1/2, open-label, multicenter study of patients with advanced solid tumors and lymphoma (NCT05358379).2 This study is exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, pharmacogenomics, and efficacy of CYC140 in patients who have progressed after receiving standard therapy or for which no standard therapy exists.2

As coprimary end points, the phase 1/2 study is evaluating the maximum-tolerated dose of CYC140, according to the incidence rate of DLTs, as well as the overall response rate. The secondary end points of the study are the type, frequency, and severity of adverse events, pharmacokinetic measurements, disease control rate, duration of response, progression-free survival, and overall survival. The study is also exploring pharmacodynamics and pharmacogenomics.

Patients aged 18 years of older with histologic or cytological confirmation of advanced cancer are eligible to enroll in the study given they also have an ECOG performance score of 0-2 and are not pregnant. Patients enrolled are required to comply with the protocol of the study, use contraception throughout, and be able to take orally administered medication.

The study excludes individuals who have a history of brain metastases with 4 weeks, conditions that affect gastrointestinal absorption, impaired cardiac function or clinically significant cardiac disease, and other conditions that may interfere with the safety and/or effectiveness of study treatment. In addition, patients cannot have received vaccines for severe acute respiratory syndrome-corona virus-2, nor chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 3 weeks. Patients must also be 4 weeks post major surgery or surgical therapy to enroll.

During the phase 1 portion of the study, patients will be administered escalating doses of CYC140 starting at 5 mg once daily. Subsequent cohorts will receive escalating doses on an escalating dose schedule until the optimal phase 2 dose is found. In the phase 2 portion, patients will receive the recommended phase 2 does of the drug in 28-day cycles.

This investigation will involve approximately 330 patients with advanced solid tumors and lymphomas in the United States, Korea, and Spain. The study is actively recruiting at all study sites.


1. A phase I study of CYC140, a PLK-1 inhibitor, in advanced leukemias or MDS. ClinicalTrials.gov. Updated April 25, 2022. Accessed September 15, 2023. https://tinyurl.com/3m253su8

2. A study to investigate CYC140, in subjects with advanced solid tumors and lymphoma. ClinicalTrials.gov. Updated October 19, 2022. Accessed September 15, 2023. https://tinyurl.com/4j9j3uhn

3. Moureau S, MacKay C, Saladino C, et al. Abstract 4178: The novel PLK1 inhibitor, CYC140: Identification of pharmacodynamic markers, sensitive target indications and potential combinations. Cancer Res. 2017;77(suppl 13):4178. doi:10.1158/1538-7445.AM2017-4178

Related Videos
Related Content