Benzinga | Nov 5, 2021 09:46AM EDT

Cyclacel Announces Dosing Of First Patient In Phase 1/2 Study Of Oral Fadraciclib In Patients With Leukemias Or Myelodysplastic Syndromes

Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC, NASDAQ:CYCCP, &quot, , Cyclacel&quot, , or the &quot, , Company&quot, , ))))), a biopharmaceutical company developing innovative medicines based on cancer cell biology, announced dosing of the first patient in the Company's multi-cohort Phase 1/2 study of oral fadraciclib in patients with leukemias or myelodysplastic syndromes (MDS).



"We are proud to have achieved this second key clinical milestone and corporate objective following the start of the oral fadraciclib Phase 1/2 solid tumor and lymphoma study last quarter," said Spiro Rombotis, Cyclacel's President and Chief Executive Officer. "After opening these two streamlined, registration-directed Phase 1/2 studies with fadraciclib as planned, we will next evaluate the clinical potential of oral CYC140, our PLK1 inhibitor, first in solid tumors and lymphomas and then in leukemias. We look forward to providing periodic updates on our clinical progress and data from these open-label studies when available."

"We are pleased to have dosed the first patient in this leukemia study and are delighted by the enthusiasm and strong interest from current and prospective investigators," said Mark Kirschbaum M.D., Senior Vice President and Chief Medical Officer of Cyclacel. "The study has initially opened at City of Hope, a world-renowned cancer research and treatment organization, with more sites to join later. We are building a distinguished, global network of participating institutions for this leukemia study, the ongoing solid tumor clinical study and also for preclinical collaborations. We are excited to begin this second mid-stage study of fadraciclib with the objective of registration-enabling outcomes as a single agent and in relevant combinations, potentially offering a new treatment option for patients with leukemias, MDS and related disorders."

"Based upon the mechanism of action and prior clinical activity shown to date, further exploration of this novel CDK2/9 inhibitor, both as a single-agent and in combinations, is warranted across a number of leukemias and MDS," said Brian Ball, M.D., Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope. "We look forward to enrolling patients in this trial, performing correlative studies, and evaluating potential treatment benefit for this experimental therapy, particularly in novel subsets of AML, which we have recently described and which may respond to inhibition of these targets."

The Phase 1/2 registration-directed trial, designated CYC065-102, uses a streamlined design and will first determine the recommended Phase 2 dose (RP2D) for single-agent, oral fadraciclib. Once RP2D has been established, the trial will immediately enter into proof-of-concept, cohort stage, using a Simon 2-stage design, where fadraciclib, both as a single agent and in combinations, will be administered to patients in up to seven cohorts relevant to the drug's mechanism of action and informed by the clinical activity of fadraciclib in previous studies.

Single-agent cohorts will include patients with acute myeloid leukemia (AML) or MDS who have an inadequate response or have progressed on venetoclax combinations with hypomethylating agent (HMA) or low dose Ara C; relapsed/refractory AML or MDS patients with FLT3, KIT or MAPK pathways (including N and K RAS, BRAF, PTPN11, NF1). The trial will also include patients with chronic lymphocytic leukemia (CLL) who have progressed after at least two lines of therapy including a BTK inhibitor and venetoclax.

Combination cohorts for patients with AML or MDS are: fadraciclib and azacitidine for patients with AML or MDS who progressed with hypomethylating (HMA) treatments and also fadraciclib and venetoclax for patients that have progressed after venetoclax therapy. A further combination cohort of fadraciclib and venetoclax will enroll patients with CLL or small lymphocytic lymphoma (SLL) who have progressed after venetoclax therapy. An additional basket cohort will evaluate patients with biomarkers relevant to the drug's mechanism, including MCL1 and MYC.

The protocol allows for expansion of a cohort based on response which may allow acceleration of the clinical development and registration plan for fadraciclib.