Cyclacel Completes Enrollment in Biomarker-Enriched Phase 2 Study

Cyclacel Pharmaceuticals, a biopharmaceutical company focused on developing innovative cancer treatments, has completed the enrollment of 12 patients in Cohort 8 of its Phase 2 study of fadraciclib, a CDK2/9 inhibitor. The study, known as 065-101, targets patients with advanced solid tumors and lymphoma. Enrollment for Cohort 5, which includes patients with T-Cell Lymphoma, is still in progress. A key aspect of this study is that patients are preselected for abnormalities in CDKN2A and/or CDKN2B.

Spiro Rombotis, President and CEO of Cyclacel, stated that the rapid enrollment over approximately six months demonstrates the significant unmet medical needs of cancer patients with these specific genetic abnormalities. The company plans to present updated safety and efficacy data at the upcoming 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA 2024) scheduled for October.

Brian Schwartz, M.D., the interim Chief Medical Officer, expressed gratitude to the patients, their families, and the international investigator group for their support in reaching the enrollment target for Cohort 8. He highlighted that a Phase 2 patient with squamous cell cancer and CDKN2A abnormalities has shown stable disease and tumor shrinkage after two cycles of fadraciclib oral tablets. Additionally, previous data from ASCO 2024 indicated a 22% reduction in tumor burden in a patient with squamous non-small cell lung cancer (NSCLC) and CDKN2A/B abnormalities after four weeks of treatment according to RECIST 1.1 criteria. More comprehensive data will be reported as additional patients from Cohort 8 undergo scans and follow-up evaluations.

The 065-101 Phase 2 study aims to assess the safety and efficacy of oral fadraciclib across eight cohorts defined by specific histology and biomarkers. These cohorts include various cancers such as endometrial, ovarian, cholangiocarcinoma, biliary tract, hepatocellular, breast, T-Cell lymphoma, B-Cell lymphoma, and colorectal cancers. Cohort 8 specifically targets patients with CDKN2A and/or CDKN2B abnormalities. The study employs a Simon 2-stage design to demonstrate responses in molecular subtypes suggested by Phase 1 data.

In the earlier Phase 1 dose-escalation part of the study, 48 patients with advanced solid tumors and lymphoma were treated with oral fadraciclib as monotherapy. The recommended Phase 2 dose (RP2D) was established as 100mg twice daily for five days per week over a four-week cycle. Notable single-agent activity, including complete responses, partial responses, and stable disease, was observed in patients with advanced endometrial, squamous NSCLC, and T-cell lymphoma. Signals of activity were also noted in patients with advanced cervical, hepatocellular, ovarian, and pancreatic cancers.

Cyclacel believes that inhibiting both CDK2 and CDK9 with fadraciclib could be more effective than targeting either kinase alone. The oral formulation of fadraciclib allows for repeat dosing, leading to transient suppression of anti-apoptotic proteins, with generally good tolerability and no severe hematological toxicity in the first treatment cycle.

CDKN2A and CDKN2B abnormalities, primarily deletions or loss of function, are common in over 40% of several solid tumors, including glioma, head and neck, pancreatic, esophageal, lung, bladder, and melanoma. CDKN2B deletions are also prevalent in over 30% of similar solid tumors.

Cyclacel Pharmaceuticals is committed to advancing its pipeline of novel cancer medicines, focusing on cell cycle, transcriptional regulation, and mitosis biology. The company’s strategy is to establish a diversified biopharmaceutical business addressing both oncology and hematology indications through its innovative drug candidates.