A Study to Investigate CYC140, in Subjects With Advanced Solid Tumors and Lymphoma

NCT ID: NCT05358379

Last Updated: 2024-02-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-14
• Study Completion Date: 2025-11-30

Brief Summary

This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, pharmacogenomics, and efficacy of CYC140 administered orally daily. 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: Bladder cancer

Group 2: Breast cancer: Triple-negative breast cancer (TNBC)

Group 3: Lung cancer (non-small cell lung cancer [NSCLC] and small cell lung cancer [SCLC])

Group 4: Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC)

Group 5: Metastatic colorectal cancer (mCRC) including KRAS-mutated mCRC

Group 6: B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL)

Group 7: T-cell lymphoma (cutaneous T-cell lymphoma [CTCL] and peripheral T-cell lymphoma [PTCL])

Group 8: Basket cohort: tumor types that are suspected to have a related mechanism of action but are not included in previous groups including, esophageal, prostate, ovarian and pancreatic cancers

Conditions

Solid Tumor, Adult Lymphoma

Study Design

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

Study Groups

Phase 1 Dose Escalation

Phase 1 = CYC140 administered orally in escalating doses starting at 5mg QD M-F week 1 to 3 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.

Group Type: EXPERIMENTAL

CYC140

Intervention Type: DRUG

CYC140 is a highly selective, orally- and intravenously- available, ATP-competitive inhibitor of PLK1.

Phase 2

Phase 2 = Recommended CYC140 phase 2 dose and schedule administered orally in 28-day cycles.

Group Type: EXPERIMENTAL

CYC140

Intervention Type: DRUG

CYC140 is a highly selective, orally- and intravenously- available, ATP-competitive inhibitor of PLK1.

Interventions

CYC140

CYC140 is a highly selective, orally- and intravenously- available, ATP-competitive inhibitor of PLK1.

Intervention Type: DRUG

Eligibility 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

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 0-2.

4. Subjects who relapsed post-autologous or post-allogeneic transplant are eligible. Post-transplant subjects must be without active fungal disease or significant acute graft-versus-host disease

5. 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.

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.

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 severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) and have suspected signs and symptoms of the novel coronavirus infection (COVID-19) or have confirmed COVID-19.

3. Subjects with a history of another primary malignancy, other than:

1. In situ carcinomas, 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 CYC140.

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

Locations

City of Hope

Duarte, California, United States

Site Status: RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 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

Miguel Villalona-Calero, MD

Role: primary

mvillalona@coh.org

Julie Urban

Role: primary

IDDCreferrals@upmc.edu

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

CYC140-101

Identifier Type: -

Identifier Source: org_study_id