Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

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.

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

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

CYC140

Mark H Kirschbaum, MD

Julius Huang, PhD

Miguel Villalona-Calero, MD

Julie Urban

Meng Gao

Do-Youn Oh, Prof. MD

Elena Garralda Cabanas, MD

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.

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

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

A Phase 1/2, Open-label, Multicenter Study to Investigate the Safety, Pharmacokinetics, and Efficacy of CYC140, an Oral PLK1 Inhibitor, in Subjects With Advanced Solid Tumors and Lymphoma

Pharmacodynamic response to CYC140 will be assessed by mRNA sequencing of blood samples to determine differential expression of PLK1 target genes (including MYC, PLK1, CDKN1A) relative to baseline.

Genomic alterations will be assessed by next generation sequencing (NGS) at baseline and various time points during treatment with CYC140 in order to investigate the relationship between genetic alterations in CYC140 related pathways and response to CYC140.

Parameters of genetic variations (DNA mutations) and copy number variations using plasma cell-free DNA derived from peripheral blood will be assessed.

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

Assessment of response criteria according to RESIST, Lugano or mSWAT.

Type, frequency, and severity of adverse drug reactions

To evaluate the disease control rate (DCR) in subjects receiving CYC140.

To evaluate the duration of response (DOR) in subjects receiving CYC140.

To evaluate progression-free survival (PFS) in subjects receiving CYC140.

To evaluate overall survival (OS) in subjects receiving CYC140.

Cyclacel Pharmaceuticals, Inc.

Symptoms and General Pathology

Syndrome

Leukemia

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

CYC140 will be administered as a single agent on Day 1 and Day 8 of each 3 week cycle

Mark Kirschbaum, MD

Hind Alazzawi

Gautam Borthakur, MD

A Phase I Pharmacologic Study of CYC140, a polo-like kinase 1 inhibitor, in Patients with Advanced Leukemias or Myelodysplastic Syndromes

This is a First in Human, open-label, single arm, dose escalation study in patients with advanced leukemias or myelodysplastic syndromes. Patients will receive CYC140 as a 1 hr infusion once a week for 2 weeks followed by 1 week of rest on an outpatient basis. One treatment cycle is 3 weeks.

One to three patients will be entered at a given dose level of CYC140. During the first cycle, all patients will be evaluated for DLTs. If DLT occurs, additional patients (up to 3) will be dosed at that dose. If no additional DLTs observed, dose escalation will continue per protocol. If a DLT does occur, dose escalation will be stopped. At least 6 patients will be treated at the RD to confirm its tolerability.

A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS

A Phase I Pharmacologic Study of CYC140, a Polo-like Kinase 1 Inhibitor, in Patients With Advanced Leukemias or Myelodysplastic Syndromes

plasma drug exposure area under the curve (AUC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Investigate CYC140, in Subjects With Advanced Solid Tumors and Lymphoma	NCT05358379	Solid Tumor, Ad...	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS	NCT03884829	AML, Adult Myelodysplastic... ALL, Adult CML, Refractory CLL, Refractory	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS	NCT03884829	AML, Adult Myelodysplastic... ALL, Adult CML, Refractory CLL, Refractory	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for cyc140

Every month we try and update this database with for cyc140 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cyc140

Every month we try and update this database with for cyc140 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cyc140 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.