Endometrial cancer, Ovarian cancer, Biliary tract cancer, Hepatocellular carcinoma, B-cell lymphoma, T-cell lymphoma, Metastatic colorectal cancer, Breast cancer (metastatic HER-2 refractory, Hormone receptor +, HER-2 negative, and MBC post-CDK4/6 inhibitor, Triple-negative) Basket cohort: tumor types that are suspected to have a related mechanism of action and are not included in previous groups MedDRA version: 21.0 Level: LLT Classification code 10014735 Term: Endometrial cancer NOS System O
Conditions
Interventions
Product Name: Fadraciclib
Product Code: CYC065
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Fadraciclib
CAS Number: 1315571-33-5
Current Sponsor code: CYC065
Concentration unit: mg milligra
Sponsors
Cyclacel Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females aged = 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 3. ECOG performance status of 0 or 1 4. Subjects must have laboratory values as stated in the protocol 5. Women of childbearing potential (WOCBP) must have a negative pregnancy test 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 6. 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. 7. Able to agree to and sign the informed consent and to comply with the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 106 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 248
Exclusion criteria
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, please see additional details in the protocol. 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. See additional details in the protocol. 5. Diseases that significantly affect GI absorption of fadraciclib 6. Subjects who have impaired cardiac function or clinically significant cardiac disease, see additional details in the protocol. 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). In subjects with a history of HBV, hepatitis B core antibody testing is required and if positive, then HBV DNA testing will be performed, and if positive, the subject will be excluded. For subjects with HCV Ab positive, HCV viral load must be below the limit of quantification. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: To determine the maximum-tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of fadraciclib when administered orally twice daily (BID) in 28-day cycles in adult subjects with advanced solid tumors and lymphoma Phase 2: To evaluate preliminary efficacy of fadraciclib as measured by overall response rate (ORR) in 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;Secondary Objective: Phase 1: - To assess safety and tolerability of fadraciclib - To investigate clinical pharmacokinetics (PK) of fadraciclib - To evaluate overall response rate (ORR) in subjects receiving fadraciclib Phase 2: - To assess the safety and tolerability of fadraciclib - To evaluate the ORR in subjects receiving fadraciclib;Primary end point(s): Phase 1: The incidence rate of dose-limiting toxicities (first cycle only) at each dose level Phase 2: ORR according to Response Evaluation Criteria in Solid Tumors: RECIST guidelines (Lugano Criteria for lymphoma, mSWAT for CTCL) for each tumor type;Timepoint(s) of evaluation of this end point: At predetermined time points described in the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety - Disease control rate (DCR) - Response rate as per Lugano Criteria for lymphoma, mSWAT for CTCL - Progression-free survival - Duration of response - Overall survival - PK in Phase 1;Timepoint(s) of evaluation of this end point: At predetermined time points described in the protocol | — |
Countries
Korea, Republic of, Spain, United States
Contacts
Public ContactJulius Huang
Cyclacel Pharmaceuticals
Outcome results
None listed