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

NCT04983810 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: CYC065-101
• Study Type: interventional
• Target: 330
• Locations: 3 countries
• Sites: 4

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.

Conditions

Solid Tumor, Adult; Lymphoma

Keywords

Solid tumor; lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  The incidence rate of dose-limiting toxicities (first cycle only) at each dose level

  6 months

• Overall Response Rate (ORR)

  Assessment of response criteria according to RESIST, Lugano or mSWAT

  18 months

Secondary Outcomes (5)

• Adverse events

  24 months

• AUC

  6 months

• Cmax

  6 months

• Tmax

  6 months

• T1/2

  6 months

Other Outcomes (2)

• Pharmacodynamics

  6 months

• Pharmacogenomics

  24 months

Study Arms (1)

Phase I Dose escalation

EXPERIMENTAL

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

Interventions

Fadraciclib DRUG

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

Also known as: CYC065

Phase I Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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
• For Phase 1, all tumor types may be enrolled
• For Phase 2, subjects will be enrolled as per the study design section above
• ECOG performance status of 0 or 1
• 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.
• 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.
• Able to agree to and sign t he informed consent and to comply with the protocol.

You may not qualify if:

• 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.
• 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.
• Subjects with a history of another primary malignancy, other than:
• Carcinomas in situ, e.g., breast, cervix, and prostate
• Locally excised nonmelanoma skin cancer
• No evidence of disease from another primary cancer for 2 or more years and has not taken any anti-cancer treatment in 2 years.
• 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.
• Diseases that significantly affect GI absorption of fadraciclib.
• Subjects who have impaired cardiac function or clinically significant cardiac disease.
• Presence of active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment
• Presence of an active infection requiring intravenous antibiotics
• Presence of known history of human immunodeficiency virus-1/2 with uncontrolled viral load and on medications that may interfere with metabolism
• Presence of active hepatitis B virus (HBV) or hepatitis C virus (HCV).
• 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.
• Major surgery/surgical therapy for any cause within 4 weeks of the first dose

Sponsors & Collaborators

• Cyclacel Pharmaceuticals, Inc.: lead

Study Sites (4)

City of Hope

Duarte, California, 91010, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Spain

RECRUITING

MeSH Terms

Conditions

Lymphoma

Interventions

CYC065

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mark H Kirschbaum, MD

  Cyclacel Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Mark H Kirschbaum, MD

CONTACT

626-316-3394; mkirschbaum@cyclacel.com

Julius Huang, PhD

CONTACT

jhuang@cyclacel.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation in Phase 1 part.

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: July 30, 2021
• Study Start: July 12, 2021
• Primary Completion: April 30, 2025
• Study Completion: June 30, 2025
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); KR (1); ES (1)