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Investigators are evaluating treatment with fadraciclib (CYC065), an oral CDK 2/9 inhibitor, in patients with advanced solid tumors and lymphoma in a phase 1/2 trial (NCT04983810).1
Fadraciclib is a highly selective second generation amino-purine inhibitor of CDK2 and CDK9 that is orally- and intravenously- available.2
The open-label, multicenter study plans to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, PGx, and efficacy of fadraciclib when given to patients orally twice a day. The study consists of 2 parts with phase 1 and phase 2 components.2
About the Phase 1/2 Study
Trial Name: A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK 2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma
ClinicalTrials.gov Identifier: NCT04983810
Sponsor: Cyclacel Pharmaceuticals, Inc
Recruitment Contact: TMark H Kirschbaum, MD, 626-316-3394, firstname.lastname@example.org or :Julius Huang, PhD, email@example.com
Completion Date: December 31, 2023
The first phase of the study will consist of a dose-escalation and a dose-finding component, and phase 2 will include patients with locally advanced, recurrent, or metastatic, histologically confirmed advanced solid tumors or lymphoma, who have failed all standard therapies or for whom standard therapy does not exist.1 In phase 2, patients will be enrolled into 8 groups, including endometrial or ovarian cancer, biliary tract cancer, hepatocellular carcinoma, breast cancer, B-cell lymphoma, T-cell lymphoma, metastatic colorectal cancer, and a basket cohort of tumor types suspected to have a related mechanism of action such as MCL1, MYC, or CCNE amplification/overexpression not included in previous groups.
Within phase 1, fadraciclib will be administered orally in escalating doses starting at 50 mg BID on Monday, Wednesday, and Friday for 3 weeks of a 4-week cycle. Then, cohorts will escalate in dose and schedule until the phase 2 dose and schedule is determined. Phase 2 of the study will give patients fadraciclib at the recommended phase 2 dose and schedule orally in 28-day cycles.
Inclusion in the study is open to patients aged 18 years and older with histologically or cytologically confirmed advanced cancer who have progressed on standard therapy or for whom no standard anticancer therapy exists. Patients must have an ECOG performance status of 0-1, be able to swallow and retain orally administered medication, and not have clinically significant gastrointestinal abnormalities that may alter the absorption. Additionally, women of childbearing potential must provide a negative pregnancy test within 7 days before the start of treatment, and male and female patients must use effective contraception during the duration of the study and for 6 months after the last dose.
The study will exclude patients with a history of brain metastases, patients who have signs associated with brain metastases and have not been assessed with radiologic imaging to rule out their presence, those who have not received vaccines for SARS-COV-2 within last 3 months and have suspected signs and symptoms of COVID-19, and patients with a history of another primary malignancy, excluding carcinomas in situ, locally excised nonmelanoma skin cancer, and those with no evidence of disease from another primary cancer for 2 or more years and has not taken any anti-cancer treatment in 2 years.
Patients with other clinically significant acute or chronic medical or psychiatric conditions, any laboratory abnormality that may increase the risk associated with the administration of treatment or may interfere with the interpretation of results from the study, and impaired cardiac function or clinically significant cardiac disease will also be excluded from the trial. Presence of active chronic inflammatory bowel disease within 6 months of enrollment, active infection requiring intravenous antibiotics, history of human immunodeficiency virus-½, active hepatitis B virus or hepatitis C virus, are also grounds for exclusion. Patients must also not have received chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 3 weeks before starting the first dose of the study drug on day 1, have not recovered from the adverse effects, and major surgery/surgical therapy for any cause within 4 weeks of the first dose.
The primary end points of the study are maximum-tolerated dose and overall response rate, and secondary end points include adverse events and pharmacokinetics. Other end points being evaluated include pharmacodynamics and pharmacogenomics.
Patients are actively being recruited for the study at City of Hope in California and MD Anderson Cancer Center in Texas, as well as in Korea, Spain.
1. A study to investigate fadraciclib (CYC065), in subjects with advanced solid tumors and lymphoma. ClinicalTrials.gov. Updated April 4, 2022. Accessed August 9, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04983810
2. Transcriptional Regulation. Cyclacel. Accessed August 9, 2023. https://cyclacel.com/our-science/fadraciclib/