Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer

NCT05450965 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2412GCCC ; HP-00109457R01CA273216-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II clinical trial will study the safety and efficacy of onvansertib to treat patients with small cell lung cancer (SCLC) who have either not responded to or are unable to tolerate chemotherapy. Onvansertib is a drug that inhibits polo-like kinase 1 (PLK-1), an enzyme that is over-expressed in many cancer cells and is involved in cellular repair.

Conditions

Small-cell Lung Cancer; Small Cell Lung Carcinoma

Keywords

Lung Cancer; Onvansertib; Polo-like Kinase; PLK1; Salvage Therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The proportion of patients having either a complete response (CR) or partial response (PR) (as best response), per RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

  Up to 42 months (cohort)

Secondary Outcomes (3)

• Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 3.5 years

• Progression-free survival (PFS)

  Up to 3.5 years

• Overall survival (OS)

  Up to 3.5 years

Study Arms (1)

Single Treatment Arm

EXPERIMENTAL

Onvansertib

Drug: Onvansertib

Interventions

Onvansertib DRUG

Onvansertib at a dose of 15 mg/m2 orally on Days 1-14 of a 21-day cycle. Treatment will continue until disease progression or intolerable toxicity.

Single Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed small cell lung cancer
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. See Section 8for the evaluation of measurable disease.
• Patient must have failed or found to be intolerant of standard frontline platinum-based regimens and not more than two lines of cytotoxic chemotherapy treatment in total for extensive stage disease. Maintenance immunotherapy counts as part of the frontline therapy, while prior chemotherapy for limited stage disease will not count toward this total if completed more than 12 months before initiation of protocol therapy. Retreatment with the original chemotherapy regimen for sensitive relapsed SCLC counts as a separate line of treatment.
• Adult patients with age \>18 years. Because no dosing or adverse event data are currently available on the use of arsenic trioxide in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
• Ability to tolerate oral medicine
• ECOG performance status ≤2
• Patients must have normal organ and marrow function as pre-defined
• Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
• Women of child-bearing potential and men must agree to use adequate contraception.
• Ability to understand and the willingness to sign a written informed consent document.
• Both men and women and members of all races and ethnic groups are eligible for this trial.

You may not qualify if:

• Treatment with chemotherapy (within 4 weeks; 6 weeks for nitrosoureas or mitomycin C); radiotherapy or biologic agents (within 2 weeks) prior to first dose of onvansertib or those persistent, clinically significant, grade ≥2 adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents (Use of conventional external beam radiation therapy will be allowed during protocol therapy solely for palliation of localized painful lesions or bone lesions at risk of fracture provided the radiation field does not encompass any selected target lesions required for assessment).
• Patients with uncontrolled symptomatic brain metastases. Subjects with a history of central nervous system (CNS) metastases must have documentation of stable brain imaging after completion of definitive treatment and prior to first dose of Study Drug. Patients must be off or on a stable dose of corticosteroids (not more than 10mg prednisone or equivalent). Definitive treatment may include surgical resection, whole brain irradiation, and/or stereotactic radiation therapy.
• Patients with active GI disorders likely to impair the absorption of oral medications
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to onvansertib.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient with untreated or active HBV, HCV and HIV are ineligible. Patients on stable doses of antiretroviral for at least six months and undetectable viral load will be enrolled with prior approval of the study sponsor. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients who require ongoing treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug.
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Cardiff Oncology: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

ACTIVE NOT RECRUITING

Related Publications (1)

• Zhang G, Pannucci A, Ivanov AA, Switchenko J, Sun SY, Sica GL, Liu Z, Huang Y, Schmitz JC, Owonikoko TK. Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer. Cancers (Basel). 2025 Jan 28;17(3):446. doi: 10.3390/cancers17030446.

  PMID: 39941812 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Interventions

onvansertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Taofeek Owonikoko, MD, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amelia Barkman, MHA

CONTACT

410-328-5009; amelia.barkman@umm.edu

Maha Khalil

CONTACT

410-328-5009; Mkhalil@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 11, 2022
• Study Start: July 19, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)