Cyclacel Unveils New Data on Fadraciclib at 2024 ASCO Meeting

Cyclacel Pharmaceuticals, Inc., a biopharmaceutical company focused on cancer treatments, revealed new clinical data on their investigational drug fadraciclib. These results emerged from the CYC065-101 study and were showcased at the American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago from May 31 to June 4, 2024.

The study assesses fadraciclib, an oral CDK2/9 inhibitor, as a monotherapy in patients with advanced solid tumors and lymphomas. Notably, this study observed clinical benefits in patients who had previously undergone multiple treatments for various cancers, including endometrial, lung, ovarian, pancreatic cancers, and T-cell lymphoma.

Spiro Rombotis, President and CEO of Cyclacel, expressed excitement over the data, highlighting the potential association between the drug's activity and alterations in tumor suppressor genes. This hypothesis is being further tested in the study's Phase 2 segment. Brian Schwartz, M.D., interim Chief Medical Officer, echoed optimism about the drug's safety and efficacy, stressing the continuation of its development in the proof of concept phase.

The Phase 1 dose escalation part of the study involved 47 heavily pretreated patients. Results indicated that fadraciclib was generally well-tolerated, with common adverse events including nausea, vomiting, diarrhea, fatigue, and hyperglycemia. Serious adverse events (SAEs) were reported in eight patients, but none at the highest dose level tested (100 mg bid, five days per week, for four weeks), which has been selected for Phase 2.

Pharmacokinetic (PK) data revealed dose-proportionality with levels exceeding preclinical efficacy targets for CDK2 and CDK9. Pharmacodynamic (PD) evaluations showed suppression of CDKN2A/B in peripheral blood within four hours post-treatment in patients receiving 100 mg bid or higher.

Evaluating 34 patients with measurable target lesions, the study noted two partial responses in patients with T-cell lymphoma, with one patient exhibiting CDKN2A loss. Additional clinical benefits were observed in patients with endometrial, ovarian, pancreatic cancers, and a patient with squamous non-small cell lung cancer, showing a 22% tumor burden reduction at four weeks per RECIST 1.1 criteria.

Currently, the study is enrolling patients with CDKN2A/B loss or T-cell lymphoma for its Phase 2 proof of concept segment, aiming to further determine the drug's efficacy and safety. Fadraciclib's development is part of Cyclacel's broader strategy to innovate cancer treatments through an understanding of cell cycle and transcriptional regulation.

Cyclin-dependent kinases (CDKs) are crucial for cell cycle control and transcriptional regulation. Dysregulation of CDKs is associated with cancer characteristics such as uncontrolled cell proliferation and increased survival. Fadraciclib, by inhibiting CDK2 and CDK9, aims to induce cancer cell death.

In earlier studies, fadraciclib showed promising results, including complete responses and stable disease in patients with various advanced cancers. One notable case from a prior Phase 1 study involved a heavily pretreated endometrial cancer patient achieving a confirmed complete response and maintaining treatment for approximately three years.

The 065-101 study is an ongoing Phase 1/2 trial for advanced solid tumors and lymphoma, actively enrolling patients with specific biomarkers. Cyclacel's broader vision includes developing a diverse biopharmaceutical portfolio targeting oncology and hematology indications through novel drug candidates.