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.

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

The initial dose of HLX51 is 0.3mg/kg, and 5 dose levels are designed: 0.3 mg/kg, 1 mg/kg , 2.5mg/kg, 5mg/kg, and 10mg/kg (Q3W). Patients with good tolerability and well controlled disease will receive the treatment until progressive disease (PD) without any clinical benefit, initiation of other anti-tumor therapies, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).

anti-OX40 tetravalent agonistic humanized monoclonal antibody

HLX51

This study is a first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas.

This study is the first-in-class open-label phase I human clinical study to evaluate the safety and tolerability of HLX51 with escalated doses in the treatment of patients with advanced/metastatic solid tumors or lymphomas. In this study, 3 + 3 dose escalation method will be adopted, and the patients will be given different doses of HLX51 intravenously. Observation period of DLT lasts for 3 weeks after the first administration of HLX51.

Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 in Patients With Solid Tumor or Lymphoma

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 (Anti-OX40 Monoclonal Antibody) in Patients With Advanced/Metastatic Solid Tumor or Lymphoma

DLT refers to the AEs that are determined to be related to the investigational product by the investigator, whose severity will affect the escalation of dose level. In this study, the DLT observation period lasts for 3 weeks after the first administration of HLX51

MTD refers to the highest dose at which less than 1/3 of subjects in the same dose group develop DLT in cycle 1 of the dose escalation stage.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Investigate CYC140, in Subjects With Advanced Solid Tumors and Lymphoma	NCT05358379	Solid Tumor, Ad...	CYC140	18 Years -	Cyclacel Pharmaceuticals, Inc.
Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX51 in Patients With Solid Tumor or Lymphoma	NCT05788107	Solid Tumor, Ad...	HLX51	18 Years -	Shanghai Henlius Biotech

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