Small-cell Lung CancerPhase 2NCT05450965
Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer
A Phase 2 study testing Onvansertib in people with Small-cell Lung Cancer and Small Cell Lung Carcinoma, run by University of Maryland, Baltimore at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small-cell Lung Cancer, Small Cell Lung Carcinoma
- What is being tested?
- Onvansertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Jul 2022to 30 Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Recruiting
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Taofeek Owonikoko, MD, PhD
Taofeek Owonikoko, MD, PhD
- Active, not recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase 2 Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer
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.
Read the detailed description
This is a single arm, two stage, phase II study of onvansertib in patients with relapsed SCLC who have received not more than 2 lines of prior therapies. The study will enroll 15 patients in stage I. Enrolment into stage II will occur if two or more patients achieve objective response. Subsequent enrolment into stage II will be by biomarker selection if the stage I accrual supports any of the three preliminarily nominated biomarkers i.e., TP53 mutation type, SCLC-Y or MYC expression. In order to establish the safety and tolerability of onvansertib at the dose of 15 mg/m2 on D1-D14 of a 21-day cycle, the first 6 participants will be closely monitored as a safety a run-in. Full safety evaluation will be conducted after all 6 patients have completed at least 1 cycle of therapy. A lower dose of onvansertib will be considered, and schedule of onvansertib as per the planned dose modification strategy, if during the safety run-in there are any deaths not clearly attributable to the underlying disease or extraneous causes or for Grade 4 hematologic or non-hematologic adverse events (AEs) occurring in 2 or more patients. In the event that a dose de-escalation is necessary following the initial safety run-in cohort, the run-in procedure will be repeated for the reduced dose level as described above. The study will continue to enroll to stage I at the dose established to be safe from the safety run-in cohort. Patients treated at the established dose in the safety run-in phase will count toward the total stage I accrual goal of 15 patients.
- Conditions
- Small-cell Lung Cancer, Small Cell Lung Carcinoma
- Being tested
- Onvansertib
- Keywords
- Lung Cancer, Onvansertib, Polo-like Kinase, PLK1, Salvage Therapy
- Medical subject headings
- Small Cell Lung Carcinoma, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OnvansertibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single Treatment Arm | Experimental | Onvansertib Receives: Drug: Onvansertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 42 months (cohort)
Secondary outcomes (3)
Adverse Events (AEs) and Serious Adverse Events (SAEs)
The number of patients incurring specific Adverse Events or Serious Adverse Events that occur from first day of treatment, considered to be possibly, probably or definitely related to study treatment, per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients experiencing multiple AEs of the same type will be reported by only the most severe grade.
Measured: Up to 3.5 years
Progression-free survival (PFS)
The median number of months from start of treatment to time of disease progression or death (from any cause), whichever occurs first. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Measured: Up to 3.5 years
Overall survival (OS)
The median number of months from start of treatment to time of death from any cause.
Measured: Up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2022
- Study start19 Jul 2022
- Primary completion31 Aug 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Small-cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Cardiff Oncology, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Taofeek Owonikoko, MD, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05450965
- Sponsor's protocol ID
- 2412GCCC ; HP-00109457
- Other IDs
- R01CA273216-01
- Status last verified
- Dec 2025
- First submitted
- 30 Jun 2022
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39941812
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05450965
- Acronym / sponsor ID
- 2412GCCC ; HP-00109457
- Conditions
- Small-cell Lung Cancer, Small Cell Lung Carcinoma
- Keywords
- Lung Cancer, Onvansertib, Polo-like Kinase, PLK1, Salvage Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Cardiff Oncology, National Cancer Institute (NCI)
- Study start
- 19 Jul 2022 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 11 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single arm, two stage, phase II study of onvansertib in patients with relapsed SCLC who have received not more than 2 lines of prior therapies. The study will enroll 15 patients in stage I. Enrolment into stage II will occur if two or more patients achieve objective response. Subsequent enrolment into stage II will be by biomarker selection if the stage I accrual supports any of the three preliminarily nominated biomarkers i.e., TP53 mutation type, SCLC-Y or MYC expression. In order to establish the safety and tolerability of onvansertib at the dose of 15 mg/m2 on D1-D14 of a 21-day cycle, the first 6 participants will be closely monitored as a safety a run-in. Full safety evaluation will be conducted after all 6 patients have completed at least 1 cycle of therapy. A lower dose of onvansertib will be considered, and schedule of onvansertib as per the planned dose modification strategy, if during the safety run-in there are any deaths not clearly attributable to the underlying disease or extraneous causes or for Grade 4 hematologic or non-hematologic adverse events (AEs) occurring in 2 or more patients. In the event that a dose de-escalation is necessary following the initial safety run-in cohort, the run-in procedure will be repeated for the reduced dose level as described above. The study will continue to enroll to stage I at the dose established to be safe from the safety run-in cohort. Patients treated at the established dose in the safety run-in phase will count toward the total stage I accrual goal of 15 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Treatment Arm | Experimental | Drug: OnvansertibOnvansertib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OnvansertibOnvansertib 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. | Drug | Single Treatment Arm |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 42 months (cohort)
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.
3 secondary outcomes
Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 3.5 years
Progression-free survival (PFS)
Time frame: Up to 3.5 years
Overall survival (OS)
Time frame: Up to 3.5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Derived from this study: PubMed 39941812Zhang 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.
- Individual participant dataSharing planned: No
Related trials for Small-cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Taofeek Owonikoko, MD, PhD principal investigator
University of Maryland, Baltimore
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Onvansertib in people with Small-cell Lung Cancer and Small Cell Lung Carcinoma, run by University of Maryland, Baltimore at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amelia Barkman, MHA (410-328-5009, amelia.barkman@umm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 42 months (cohort)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05450965, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.