Using Onvansertib to treat relapsed small cell lung cancer

A Phase 2 Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer

This study is testing a new drug called onvansertib to see if it can help people with relapsed small cell lung cancer who haven't had success with chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Maryland, Baltimore (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 2 sites (Baltimore, Maryland and 1 other locations)
• Trial ID: NCT05450965 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the safety and efficacy of onvansertib, a PLK1 inhibitor, in patients with relapsed small cell lung cancer (SCLC) who have not responded to or cannot tolerate chemotherapy. The study is designed as a single-arm, two-stage trial, initially enrolling 15 patients to assess safety and tolerability. If two or more patients show an objective response, the trial will proceed to stage II with potential biomarker selection for further enrollment. The first six participants will undergo a safety run-in to monitor for adverse events before establishing the optimal dose for the remaining participants.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically or cytologically confirmed small cell lung cancer who have measurable disease and have failed or are intolerant to standard chemotherapy.

Not a fit: Patients with limited stage disease who have not received prior chemotherapy or those with non-measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed small cell lung cancer who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in the context of relapsed SCLC, other studies targeting PLK1 have shown promise in different cancer types.

Eligibility criteria

Inclusion Criteria:

1. Patients must have histologically or cytologically confirmed small cell lung cancer
2. 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.
3. 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.
4. 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.
5. Ability to tolerate oral medicine
6. ECOG performance status ≤2
7. Patients must have normal organ and marrow function as pre-defined
8. Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
9. Women of child-bearing potential and men must agree to use adequate contraception.
10. Ability to understand and the willingness to sign a written informed consent document.
11. Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

1. 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.
2. 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).
3. 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.
4. Patients with active GI disorders likely to impair the absorption of oral medications
5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to onvansertib.
6. 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.
7. 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.
8. 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.
9. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
10. Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.

Where this trial is running

Baltimore, Maryland and 1 other locations

• University of Maryland Greenebaum Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Active_not_recruiting)

Study contacts

• Principal investigator: Taofeek Owonikoko, MD, PhD — University of Maryland, Baltimore
• Study coordinator: Amelia Barkman, MHA

Conditions Small-cell Lung Cancer; Small Cell Lung Carcinoma; Lung Cancer; Onvansertib; Polo-like Kinase; PLK1; Salvage Therapy