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Cyclacel Reports Interim Seliciclib Phase IIa Data at 2005 ASCO

Posted on: Sunday, 15 May 2005, 09:00 CDT

Cyclacel Group plc ("Cyclacel"), the cell cycle-based biopharmaceutical company, today reported interim data from a multicenter, European Phase IIa trial of its lead cancer drug candidate, seliciclib (CYC202), administered in combination with gemcitabine and cisplatin in advanced Non-Small Cell Lung Cancer (NSCLC) patients. The data was presented at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida.

Seliciclib is the leading orally-available CDK inhibitor in Phase II clinical development. It is a small molecule drug that inhibits the cell cycle targets CDK2/E, CDK2/A, CDK7/H and CDK9/T. The interim data indicated that the combination treatment did not appear to increase the frequency or severity of the known toxicities of gemcitabine and cisplatin and that the combination is active in NSCLC.

Specifically, the preliminary data presented at ASCO described the effects of seliciclib on the first 27 patients treated in this ongoing study. As expected from Phase I trials of seliciclib, patients on the combination treatment experienced seliciclib-induced adverse events of nausea, vomiting, transient elevations in serum creatinine and liver function parameters and transient hypokalemia. Among 14 patients evaluable for response, six were reported to have partial responses (PR), seven stable disease (SD) and one progressive disease (PD).

The Phase IIa interim data followed a Phase I trial of seliciclib which suggested that the drug may have antitumor activity in NSCLC. In the Phase I study two heavily pre-treated NSCLC patients that failed multiple therapies experienced prolonged disease stabilization of 13 and 18 months, respectively, after being given seliciclib as a single agent. Seliciclib was synergistic with gemcitabine in an in vivo NSCLC xenograft study.

Dr. Judy Chiao, Cyclacel's VP Clinical Development and Regulatory Affairs said, "We are pleased that the initial data from this trial demonstrates the feasibility of combining seliciclib with standard doses of gemcitabine and cisplatin and the combination appears to be active in NSCLC. Seliciclib has been administered to over 200 subjects to date and does not appear to induce myelosuppression. We expect to complete treatment of the remaining patients in this study shortly. Following analysis of the final data we will formulate our plans for the next stage of clinical development."

In a separate ASCO presentation, researchers from Dana-Farber Cancer Institute and Harvard Medical School reported preclinical data showing that seliciclib caused apoptosis in myeloma cells that were sensitive or resistant to chemotherapy in part by down regulating the anti-apoptotic gene MCL-1. The investigators also reported that combinations of seliciclib tested in vitro with either bortezomib or doxorubicin were synergistic and examination of these combinations in clinical trials is warranted.

Spiro Rombotis, Cyclacel's Chief Executive Officer, said: "These results, along with the data presented earlier on our second candidate, CYC682, underscore the steady progress we are making in advancing our clinical pipeline. The development of these drug candidates is in line with our strategy to pursue compounds with novel mechanisms that target different points within the cell cycle."

About Cyclacel (www.cyclacel.com)

Cyclacel is a biopharmaceutical company dedicated to the discovery, development and commercialization of novel, mechanism-targeted drugs to treat human cancers and other serious disorders. The company is currently evaluating seliciclib (CYC202), an orally-available Cyclin Dependent Kinase inhibitor, in Phase II clinical trials for the treatment of Non-Small Cell Lung Cancer and B-cell hematological malignancies. CYC682 is an orally-available, cell cycle modulating nucleoside analog in Phase I clinical trials for the treatment of cancer. Cyclacel has eight additional programs at preclinical stages.

Notes to Editors:

Seliciclib (CYC202, R-roscovitine) is a novel cell cycle drug belonging to the Cyclin Dependent Kinase (CDK) inhibitor class (US Patent 6,316,456). CDK inhibition is an important new approach in the quest for drugs that target the molecular mechanism of the body's own cancer stopping genes. In preclinical studies seliciclib demonstrated high specificity against cell cycle targets CDK2/E, CDK2/A, CDK7/H and CDK9/T. Seliciclib is supplied in capsules and is the first drug in its class that is available by mouth.

Phase I data suggested that seliciclib appears to be well tolerated without the typical side effects associated with current chemotherapy and may prolong Time-To-Progression in patients with various cancers. In particular two patients with heavily pre-treated Non-Small Cell Lung Cancer (NSCLC) experienced prolonged disease stabilization of 13 and 18 months, respectively, suggesting that seliciclib may have antitumor activity in NSCLC. Biomarker data showed that seliciclib is inducing cancer cell suicide or apoptosis in cancer patients.

Because CDK inhibitors act at a different part of the cell cycle than current chemotherapies, giving these drugs together as combination treatment may work synergistically. It is thought that seliciclib acts on the G1/S or early checkpoint of the cell cycle and induces cancer cells to die by committing suicide or apoptosis. Certain conventional chemotherapies, such as gemcitabine and cisplatin, exert their anticancer activity at the S-phase of the cell cycle. The potential therefore exists for combinations of G1/S- and S-phase active drugs to act in synergy and kill more cancer cells than either drug alone.

Interim Phase IIa data in patients with NSCLC receiving combination treatment of seliciclib, gemcitabine and cisplatin suggest that seliciclib causes no apparent increase in frequency or severity of the known toxicities of gemcitabine and cisplatin. Among fourteen patients evaluable for response to date, six were reported to have partial responses (PR), seven stable disease (SD) and one progression of disease (PD).

In addition to the lung cancer program seliciclib is in Phase II clinical trials in patients with B-cell hematological malignancies. Seliciclib has also completed a Phase I trial in healthy volunteers and is being explored for use in glomerulonephritis, a group of inflammatory kidney diseases caused by renal cell proliferation.

2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, 13-17 May 2005.

Abstract No. 2060: Phase IIa study of seliciclib (CYC202 or R-roscovitine) in combination with gemcitabine (gem)/cisplatin (cis) in patients with advanced non-small cell lung cancer (NSCLC). Presenter: J.H.M. Schellens, MD (Level 2, Hall C, Sunday, May 15, 2005, 8:00 - 12:00pm).

Abstract No. 6532: CYC202 (seliciclib or R-Roscovitine), a small molecule cyclin dependent kinase inhibitor, overcomes drug resistance via down-regulation of Mcl-1 in multiple myeloma (MM). Presenter: Noopur S. Raje, MD (Level 2, Hall F4, Monday, May 16, 2005, 1:30 - 5:30pm).

(C) 2005 - Cyclacel Group plc All Rights Reserved. Cyclacel(R) is a registered trademark.

Source: Business Wire

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