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A Study to Investigate Fadraciclib (CYC065), in Subjects With Advanced Solid Tumors and Lymphoma

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ClinicalTrials.gov Identifier: NCT04983810
Recruitment Status : Recruiting
First Posted : July 30, 2021
Last Update Posted : April 4, 2022
Information provided by (Responsible Party):
Cyclacel Pharmaceuticals, Inc.

Brief Summary:
This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of fadraciclib administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors and lymphoma who have progressed despite having standard therapy or for which no standard therapy exists.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Lymphoma Drug: Fadraciclib Phase 1 Phase 2

Detailed Description:

Phase 1 part of the study will consist of a dose-escalation and a dose-finding component .

Phase 2 will enroll subjects with locally advanced, recurrent, or metastatic, histologically confirmed advanced solid tumors or lymphoma, who have failed all standard therapies or for whom standard therapy does not exist, into 8 groups:

Group 1: Endometrial or Ovarian cancer

Group 2: Biliary tract cancer

Group 3: HCC

Group 4: Breast cancer, meeting any of the following criteria:

  • HER-2 refractory MBC
  • HR positive, HER-2 negative, MBC post-CDK4/6 inhibitor
  • Triple-negative breast cancer (TNBC)

Group 5: B-cell lymphoma

Group 6: T-cell lymphoma (CTCL and PTCL)

Group 7: mCRC, including KRAS mutated mCRC

Group 8: Basket cohort: Tumor types suspected to have a related mechanism of action such as MCL1, MYC or CCNE amplification/overexpression not included in previous groups.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation in Phase 1 part.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Fadraciclib (CYC065), an Oral CDK 2/9 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma
Actual Study Start Date : July 12, 2021
Estimated Primary Completion Date : October 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Phase I Dose escalation

Phase I = Fadraciclib administered orally in escalating doses starting at 50mg bid MWF for 3 weeks of a 4 week cycle. Subsequent cohorts will escalate in dose and schedule until optimized phase 2 dose and schedule is achieved.

Phase 2 = Recommended Fadraciclib phase 2 dose and schedule administered orally in 28 day cycles.

Drug: Fadraciclib
Fadraciclib is a highly selective, orally- and intravenously- available, 2nd generation amino-purine inhibitor of CDK2 and CDK9.
Other Name: CYC065

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: 6 months ]
    The incidence rate of dose-limiting toxicities (first cycle only) at each dose level

  2. Overall Response Rate (ORR) [ Time Frame: 18 months ]
    Assessment of response criteria according to RESIST, Lugano or mSWAT

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 24 months ]
    Type, frequency, and severity of adverse drug reactions

  2. AUC [ Time Frame: 6 months ]
    Fadraciclib plasma concentrations

  3. Cmax [ Time Frame: 6 months ]
    Fadraciclib plasma concentrations

  4. Tmax [ Time Frame: 6 months ]
    Fadraciclib plasma concentrations

  5. T1/2 [ Time Frame: 6 months ]
    Fadraciclib plasma concentrations

Other Outcome Measures:
  1. Pharmacodynamics [ Time Frame: 6 months ]
    To investigate CDK9-dependent transcription inhibition as assessed by differential target gene expression relative to baseline.

  2. Pharmacogenomics [ Time Frame: 24 months ]
    To investigate plasma cell-free DNA mutation and copy number variation profile of fadraciclib as determined by NGS.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria

  1. Age ≥ 18 years
  2. Subjects with histological- or cytological-confirmed, advanced cancer who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists

    1. For Phase 1, all tumor types may be enrolled
    2. For Phase 2, subjects will be enrolled as per the study design section above
  3. ECOG performance status of 0 or 1
  4. Women of childbearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug. Both males and females must agree to use effective birth control during the study (prior to the first dose and for 6 months after the last dose) if conception is possible during this interval.
  5. Subjects must be able to swallow and retain orally administered medication and not have any clinically significant GI abnormalities that may alter the absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
  6. Able to agree to and sign t he informed consent and to comply with the protocol.

Exclusion criteria

  1. Subjects with a history of brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Subjects with treated brain metastases that are asymptomatic and have been clinically stable for at least 4 weeks will be eligible.
  2. Subjects who have not received vaccines for SARS-COV-2 within last 3 months and have suspected signs and symptoms of COVID-19 or a recent history (within 14 days) of contact with any COVID-19 positive subject/isolation/quarantine or subjects with confirmed COVID-19.
  3. Subjects with a history of another primary malignancy, other than:

    1. Carcinomas in situ, e.g., breast, cervix, and prostate
    2. Locally excised nonmelanoma skin cancer
    3. No evidence of disease from another primary cancer for 2 or more years and has not taken any anti-cancer treatment in 2 years.
  4. Any other clinically significant acute or chronic medical or psychiatric condition or any laboratory abnormality that may increase the risk associated with study drug administration or may interfere with the interpretation of study results.
  5. Diseases that significantly affect GI absorption of fadraciclib.
  6. Subjects who have impaired cardiac function or clinically significant cardiac disease.
  7. Presence of active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment
  8. Presence of an active infection requiring intravenous antibiotics
  9. Presence of known history of human immunodeficiency virus-1/2 with uncontrolled viral load and on medications that may interfere with metabolism
  10. Presence of active hepatitis B virus (HBV) or hepatitis C virus (HCV).
  11. Chemotherapy, biologic therapy, targeted therapy, immunotherapy, extended-field radiotherapy, or investigational agents within 5 half-lives or 3 weeks (whichever is shorter) prior to administration of first dose of study drug on Day 1 or have not recovered from the side effects of such therapy.
  12. Major surgery/surgical therapy for any cause within 4 weeks of the first dose

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04983810

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Contact: Mark H Kirschbaum, MD 626-316-3394 mkirschbaum@cyclacel.com
Contact: Julius Huang, PhD jhuang@cyclacel.com

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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Aruna Parikh       arparikh@coh.org   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Meng Gao       mgao@mdanderson.org   
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Do-Youn Oh, Prof. MD       ohdoyoun@snu.ac.kr   
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Elena Garralda Cabanas, MD       egarralda@vhio.net   
Sponsors and Collaborators
Cyclacel Pharmaceuticals, Inc.
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Study Chair: Mark H Kirschbaum, MD Cyclacel Pharmaceuticals, Inc.
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Responsible Party: Cyclacel Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04983810    
Other Study ID Numbers: CYC065-101
First Posted: July 30, 2021    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cyclacel Pharmaceuticals, Inc.:
Solid tumor
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases