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

NCT ID: NCT04983810

Last Updated: 2024-01-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-12
• Study Completion Date: 2025-06-30

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.

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.

Conditions

Solid Tumor, Adult; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fadraciclib

Intervention Type: DRUG

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

Interventions

Fadraciclib

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

Intervention Type: DRUG

Other Intervention Names

CYC065

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cyclacel Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark H Kirschbaum, MD

Role: STUDY_CHAIR

Cyclacel Pharmaceuticals, Inc.

Locations

City of Hope

Duarte, California, United States

Site Status: RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status: RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status: RECRUITING

Countries

United States; South Korea; Spain

Central Contacts

Mark H Kirschbaum, MD

Role: CONTACT

mkirschbaum@cyclacel.com

626-316-3394

Julius Huang, PhD

Role: CONTACT

jhuang@cyclacel.com

Facility Contacts

Aruna Parikh

Role: primary

arparikh@coh.org

Meng Gao

Role: primary

mgao@mdanderson.org

Do-Youn Oh, Prof. MD

Role: primary

ohdoyoun@snu.ac.kr

Elena Garralda Cabanas, MD

Role: primary

egarralda@vhio.net

Other Identifiers

CYC065-101

Identifier Type: -

Identifier Source: org_study_id