Cyclacel Pharmaceuticals Reports New Clinical Data from Ongoing, Phase 2 Study of Oral Fadraciclib at the 2024 EORTC-NCI-AACR Symposium
Cyclacel Pharmaceuticals presented interim Phase 2 data for fadraciclib (fadra) monotherapy in advanced solid tumor patients with CDKN2A/B abnormalities at the 2024 EORTC-NCI-AACR Symposium. The study enrolled 12 patients in Cohort 8, with various cancer types including pancreatic, melanoma, and others. Out of six evaluable patients, two achieved stable disease: a melanoma patient (125 days treatment) and a squamous cell CUP patient with 11% tumor shrinkage (85+ days, ongoing). The drug showed good tolerability with no Grade 3 or higher adverse events. Two additional patients are ongoing but await first scans.
Cyclacel Pharmaceuticals ha presentato dati preliminari della Fase 2 per il trattamento monoterapico con fadraciclib (fadra) in pazienti con tumori solidi avanzati con anomalie CDKN2A/B al Simposio EORTC-NCI-AACR del 2024. Lo studio ha arruolato 12 pazienti nel Coorte 8, con vari tipi di cancro tra cui pancreatico, melanoma e altri. Di sei pazienti valutabili, due hanno raggiunto una malattia stabile: un paziente con melanoma (125 giorni di trattamento) e un paziente con CUP a cellule squamose con una riduzione tumorale dell'11% (85+ giorni, in corso). Il farmaco ha mostrato una buona tollerabilità senza eventi avversi di Grado 3 o superiori. Altri due pazienti sono in corso ma attendono le prime scansioni.
Cyclacel Pharmaceuticals presentó datos interinos de la Fase 2 para la monoterapia con fadraciclib (fadra) en pacientes con tumores sólidos avanzados con anomalías en CDKN2A/B en el Simposio EORTC-NCI-AACR 2024. El estudio incluyó 12 pacientes en el Cohorte 8, con varios tipos de cáncer, incluidos páncreas, melanoma y otros. De seis pacientes evaluables, dos lograron enfermedad estable: un paciente con melanoma (125 días de tratamiento) y un paciente con CUP de células escamosas con un 11% de reducción tumoral (85+ días, en curso). El medicamento mostró buena tolerancia sin eventos adversos de Grado 3 o superior. Dos pacientes adicionales están en tratamiento pero esperan la primera evaluación por imágenes.
사이클라셀 제약은 2024 EORTC-NCI-AACR 심포지엄에서 CDKN2A/B 이상이 있는 진행성 고형 종양 환자를 대상으로 하는 fadraciclib (fadra) 단일 요법의 중간 Phase 2 데이터를 발표했습니다. 이 연구는 다양한 암 유형인 췌장암, 흑색종 등을 포함하여 8코호트에서 12명의 환자를 등록했습니다. 평가 가능한 6명의 환자 중 2명이 안정적인 질병 상태에 도달했습니다: 한 명의 흑색종 환자(125일 치료)와 11% 종양 축소를 보인 편평세포 CUP 환자(85일 이상, ongoing)가 포함됩니다. 이 약물은 3등급 이상의 부작용 없이 좋은 내약성을 보였습니다. 두 명의 추가 환자가 계속 진행 중이며 첫 번째 스캔 결과를 기다리고 있습니다.
Cyclacel Pharmaceuticals a présenté des données intermédiaires de la phase 2 concernant la monothérapie par fadraciclib (fadra) chez des patients atteints de tumeurs solides avancées présentant des anomalies CDKN2A/B lors du Symposium EORTC-NCI-AACR 2024. L'étude a inclus 12 patients dans le Cohorte 8, avec divers types de cancer, y compris le pancréas, le mélanome et d'autres. Parmi les six patients évaluables, deux ont obtenu une maladie stable : un patient atteint de mélanome (traitement pendant 125 jours) et un patient avec CUP à cellules squameuses ayant présenté une réduction tumorale de 11% (85 jours et plus, en cours). Le médicament a montré une bonne tolérance sans événements indésirables de grade 3 ou plus. Deux patients supplémentaires sont en cours de traitement mais attendent les premiers examens par imagerie.
Cyclacel Pharmaceuticals hat beim 2024 EORTC-NCI-AACR Symposium vorläufige Phase-2-Daten zur Monotherapie mit fadraciclib (fadra) bei Patienten mit fortgeschrittenen soliden Tumoren und CDKN2A/B-Anomalien vorgestellt. Die Studie umfasste 12 Patienten in Kohorte 8, mit verschiedenen Krebsarten, einschließlich Bauchspeicheldrüsenkrebs, Melanom und anderen. Von den sechs auswertbaren Patienten erreichten zwei eine stabile Erkrankung: ein Melanom-Patient (125 Tage Behandlung) und ein Patient mit Plattenepithel-CUP mit einer Tumorzurückbildung von 11% (85+ Tage, ongoing). Das Medikament zeigte eine gute Verträglichkeit ohne Grade-3- oder höhere unerwünschte Ereignisse. Zwei weitere Patienten sind in Behandlung, warten jedoch auf die ersten Scans.
- Good tolerability profile with no Grade 3 or higher adverse events
- Stable disease achieved in 2 out of 6 evaluable patients
- 11% tumor shrinkage observed in one patient
- efficacy data with only 2 of 6 evaluable patients showing stable disease
- No complete or partial responses reported in Cohort 8
Insights
The interim Phase 2 data for fadraciclib shows mixed results with modest efficacy signals. Out of 6 evaluable patients, 2 achieved stable disease, with one showing
The biomarker-driven approach targeting CDKN2A/B abnormalities shows some potential, particularly in the melanoma patient (125-day treatment duration) and the squamous cell CUP patient (ongoing at 85+ days). However, the small patient population and immature data make it difficult to draw definitive conclusions about efficacy.
The diverse cancer types being treated (12 patients across 11 different cancers) and the heavily pretreated nature of the population (median 3 prior therapies) add complexity to interpreting the results. While the safety profile is encouraging, more mature data and larger patient cohorts will be needed to establish clinical significance.
- Interim data for fadraciclib monotherapy in patients with advanced solid tumors preselected for CDKN2A and/or CDKN2B abnormalities -
BERKELEY HEIGHTS, N.J., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative cancer medicines, today announced that initial safety and efficacy data from twelve patients with advanced solid tumors enrolled in the Phase 2 part of the 065-101 clinical study of fadraciclib, or “fadra”, as a single agent was presented as a poster at the 2024 EORTC-NCI-AACR 36th Symposium on Molecular Targets and Cancer Therapeutics (“Triple Meeting”), in Barcelona, Spain (October 23-25, 2024). The patients were enrolled in the biomarker-enriched, Cohort 8 of the proof of concept study and were preselected for CDKN2A and/or CDKN2B abnormalities.
“We are encouraged by the interim data of cohorts 6 and 8 in our Phase 2 study of fadra,” said Spiro Rombotis, President and Chief Executive Officer. “Although the data in Cohort 8 is immature with ongoing patients still to have a first scan and being followed up, we continue to see good tolerability and signals of efficacy in patients with CDKN2A/B abnormalities that have had their first scan and follow-up evaluation. We are grateful to our investigators, the patients and their families for their support of this important study.”
Interim Phase 2 Data
Fadraciclib was well tolerated in Cohort 8. Most common drug-related adverse events included diarrhea, nausea, vomiting and were similar to those seen at this dose in Phase 1. There were no Grade 3 or higher treatment-emergent adverse events in the Phase 2 study this far, consistent with the Phase 1 data. The majority of patients (12/14) had ECOG performance status of 1 and median number of prior therapies was 3.
In Cohort 8, four patients had pancreatic cancer, and one each cholangiocarcinoma, duodenal, melanoma, cervical, laryngeal, ovarian, squamous cell cancer with unknown primary (CUP) and thymus cancer. Out of six patients evaluable for efficacy, two achieved stable disease: a melanoma patient whose treatment duration was 125 days and a squamous cell CUP patient who achieved
The most common molecular characteristics of Cohort 8 patients were loss of function or deletion of CDKN2A and/or CDKN2B tumor suppressor genes. Other pharmacogenomic observations included CDKN2A/B, KRAS and/or TP53 mutations.
Study Design
Two Phase 2 dose expansion cohorts in the 065-101 study were initiated. Cohort 8 prospectively enrolled 12 patients with known CDKNA/B genetic alterations between April and September 2024. The rationale was to further evaluate observations of clinical activity in Phase 1 patients with known CDNK2A or CDKN2B genetic alterations. Cohort 6 is enrolling patients with T-cell Lymphoma with two patients treated so far. The rationale was to further evaluate observations of partial response (PR) in 2/3 Phase 1 patients with T-cell lymphoma. Certain T-Cell lymphomas are known to harbor CDNK2A genetic alterations. All patients were treated with oral fadraciclib 100mg BID, M-F, week 1-4 in 28-day cycles which was the Recommended Phase 2 dose (RP2D).
The primary objectives of the 065-101 study in the Dose Escalation stage are to determine maximum tolerated dose (MTD) and/or RP2D and in the Phase 2, Proof of Concept stage to evaluate preliminary efficacy of fadraciclib as measured by overall response rate (ORR). The secondary objectives in Dose Escalation are to assess safety and tolerability, pharmacokinetics, and ORR, while in Phase 2, Proof of Concept, to assess safety and tolerability, evaluate disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS). The study is utilizing a Simon two-stage optimal design to evaluate clinical activity. Exploratory objectives include investigation of clinical pharmacodynamics (PD) and pharmacogenomics (PGx).
Further information from the poster is available at: Link to poster
About Fadraciclib
Fadraciclib is a highly selective CDK2 (IC50=5 nM) and CDK9 (IC50=26 nM) inhibitor causing anaphase mitotic catastrophe and apoptotic death of cancer cells at sub-micromolar concentrations. Retrospective review of the dose escalation portion of Phase 1 studies suggested clinical activity in patients with known CDNK2A or CDKN2B genetic alterations. In a Phase 1 study of intravenous fadraciclib monotherapy (065-01) a heavily pretreated endometrial cancer patient with CDNK2A, CDKN2B and PRMT5 loss achieved confirmed complete response (CR).
In the Phase 1 oral fadraciclib monotherapy study (065-101), 7/38 treated patients were found to have known CDKN2A/B genetic alterations, of which 6 were evaluable for efficacy. A PTCL patient with CDKN2A P114L mutation reported a partial response (PR). A squamous cell NSCLC patient with CDKN2B loss reported stable disease (SD) and
About Cyclacel Pharmaceuticals, Inc.
Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit www.cyclacel.com.
Forward-looking Statements
This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include, among other things, statements related to the efficacy and safety profile of fadraciclib in an incomplete clinical trial, Cyclacel’s future plans and prospects, Cyclacel’s anticipated cash runway and the planned timing of data results and continued development of fadraciclib. Factors that may cause actual results to differ materially include market and other conditions, the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates and Cyclacel’s ability to regain and maintain compliance with Nasdaq’s continued listing requirements, although no assurance to that effect can be given. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10-K and other periodic and other filings we file with the Securities and Exchange Commission and are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Contact
Company: Paul McBarron, (908) 517-7330, IR@cyclacel.com
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FAQ
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