Cyclacel Pharmaceuticals, Inc. announced that new clinical, pharmacokinetic (PK) and pharmacodynamic (PD) data from the CYC065-101 study of fadraciclib as oral monotherapy was presented at a poster at the American Society of Clinical Oncology (ASCO) Annual Meeting from May 31, 2024 to June 4, 2024 in Chicago, IL. New clinical, PK and PD data were presented at ASCO from the fully enrolled, Phase 1, dose escalation part of the CYC065-101 study of fadraciclib as monotherapy (n=47). The patients were heavily pretreated, having received a median of four prior lines of therapy.

Fadraciclib was generally well tolerated with good compliance between dose levels 1 and 5. The most common treatment related adverse events reported were nausea (66.0%), vomiting (46.8%), diarrhea (31.9%) fatigue (25.5%), and hyperglycemia (21.3%). A total of 25 drug-related SAEs were reported in 8 patients, with most common being hyperglycemia (n=4), platelet count decrease (n=3), and accidental overdose (n=3). There were no drug-related SAEs at dose level 5 (100 mg bid, 5 days a week, for 4/4 weeks) which was selected for the Phase 2 proof of concept part of the 065-101 study.

PKs were dose-proportional and exceeded the preclinical efficacy targets for both CDK2 and CDK9. PDs evaluated in peripheral blood showed suppression of CDKN2A/B by four hours post treatment in most patients who received 100 mg bid or higher. A total of 34 patients had measurable target lesions at baseline.

Two partial responses were reported in patients with T-cell lymphoma, one of whom had CDKN2A loss. A squamous non-small cell lung (NSCLC) cancer patient with CDKN2A and CDKN2B loss achieved 22% reduction in tumor burden at 4 weeks per RECIST 1.1 criteria. In addition, clinical benefit was reported in two patients with endometrial cancer, and one each with ovarian and pancreatic cancers.

The proof of concept part of the study is now enrolling patients with CDKN2A/B loss or T-cell lymphoma.