Onvansertib for Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Amelia Barkman, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taofeek Owonikoko

Must not be taking: Investigational agents, Hematopoietic growth factors

Disqualifiers: Uncontrolled brain metastases, Active GI disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 42 months

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called onvansertib for individuals with small cell lung cancer who haven't responded well to chemotherapy or can't tolerate it. Onvansertib blocks an enzyme (a type of protein) that aids cancer cells in repairing themselves. The trial will assess the safety and effectiveness of this drug for patients whose cancer has not improved with standard treatments. Suitable candidates have small cell lung cancer that hasn’t improved with chemotherapy and can take oral medication. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have had chemotherapy within 4 weeks or radiotherapy within 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that onvansertib is likely to be safe for humans?

Research has shown that onvansertib may help treat small cell lung cancer (SCLC). Researchers are currently testing its safety and effectiveness. Onvansertib blocks an enzyme called PLK-1, which cancer cells need to repair and grow.

In earlier studies, onvansertib was used alone in patients with difficult-to-treat cancers like SCLC. These studies found that the drug can be taken safely. Participants generally tolerated the drug well, and serious side effects were uncommon. However, like any treatment, some side effects can occur.

The drug remains under study, so more information about its safety will emerge over time. Current evidence suggests that onvansertib is generally well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Onvansertib is unique because it targets specific enzymes called PLK1, which are often overactive in small cell lung cancer (SCLC) cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Onvansertib zeroes in on these enzymes, potentially reducing harm to healthy cells and minimizing side effects. Researchers are excited because this targeted approach might improve the effectiveness of treatment and offer a new hope for patients with SCLC, especially those who haven't responded well to standard therapies like etoposide and cisplatin.

What evidence suggests that onvansertib might be an effective treatment for small cell lung cancer?

Research has shown that onvansertib might help treat small cell lung cancer (SCLC). In a recent study, patients who took a 30mg dose of onvansertib had a 49% confirmed objective response rate (ORR), meaning nearly half experienced a noticeable reduction in tumor size. The drug blocks an enzyme called polo-like kinase 1 (PLK-1), which aids cell growth and repair. PLK-1 is often overly active in cancer cells, so inhibiting it may help prevent cancer growth. These early results suggest that onvansertib could be a treatment option for those who haven't responded well to chemotherapy. Participants in this trial will receive onvansertib as the sole treatment under investigation. ^{1 2 3 5 6}

Who Is on the Research Team?

Taofeek Owonikoko, MD, PhD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for adults over 18 with small cell lung cancer (SCLC) who have tried and not responded to or can't tolerate chemotherapy. They must be able to take oral medication, use contraception, and have a certain level of physical fitness (ECOG ≤2). People with more than two prior chemo treatments, active hepatitis B/C or HIV without approval, recent major surgery, ongoing serious illnesses, or untreated brain metastases cannot join.

Inclusion Criteria

I've had 1 or 2 chemotherapy treatments for advanced lung cancer and can't tolerate standard treatments.

I have a tumor that can be measured with a scan.

I am over 18 years old.

Exclusion Criteria

I haven't had chemotherapy, radiotherapy, or biologic agents recently.

I had major surgery less than 2 weeks ago or am still dealing with its side effects.

I am willing and able to follow the study rules and work with the research team.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial 6 participants are closely monitored to establish safety and tolerability of onvansertib at the dose of 15 mg/m2 on D1-D14 of a 21-day cycle

3 weeks

Multiple visits for monitoring

Treatment

Participants receive onvansertib treatment in a 21-day cycle, with dose adjustments based on safety evaluations

Up to 42 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Onvansertib

Trial Overview The trial is testing Onvansertib's safety and effectiveness in treating SCLC. Onvansertib blocks PLK-1 enzymes that help cancer cells repair themselves. Participants will receive this drug after failing standard platinum-based therapies and up to two lines of cytotoxic chemotherapy for extensive stage disease.

How Is the Trial Designed?

Group I: Single Treatment Arm Experimental Treatment 1 Intervention

Onvansertib

Onvansertib is already approved in United States, European Union for the following indications:

Approved in United States as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Approved in European Union as Onvansertib for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

Who Is Running the Clinical Trial?

Taofeek Owonikoko

Lead Sponsor

Trials

2

Recruited

90+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Cardiff Oncology

Industry Sponsor

Trials

12

Recruited

650+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of sorafenib when combined with carboplatin and pemetrexed was determined to be 200 mg taken twice daily, although this was based on a small sample size of only 6 patients at this dose level.

Dose-limiting toxicities (DLT) were observed in several patients, indicating that while sorafenib can be combined with standard chemotherapy regimens for lung cancer, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients. Davies, JM., Dhruva, NS., Walko, CM., et al.[2021]

Small cell lung cancer (SCLC) is a challenging disease with poor prognosis, primarily treated with platinum-based chemotherapy, but it often relapses after initial response.

Recent advances in cancer genomics have led to the development of novel anti-tumor agents, including DNA damage response inhibitors and immune checkpoint modulators, which show promise in transforming treatment strategies for SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of molecularly targeted agents and immunotherapies in small cell lung cancer. Sharp, A., Bhosle, J., Abdelraouf, F., et al.[2021]

The novel CHK1 inhibitor prexasertib showed strong effectiveness against small-cell lung cancer (SCLC) in both laboratory and animal models, indicating its potential as a targeted therapy.

Prexasertib not only worked well on its own but also enhanced the effects of other treatments like cisplatin and olaparib, especially in SCLC cases with MYC amplification, suggesting a promising approach for both platinum-sensitive and resistant forms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. Sen, T., Tong, P., Stewart, CA., et al.[2021]

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer, and while first-line therapies are effective initially, resistance develops almost universally, highlighting the need for better treatment options.

New treatments like ONC201, which activates the cellular stress response and induces apoptosis, are showing promise in early clinical testing, and its combination with lurbinectedin is being explored to improve outcomes for SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of Biomarker-Driven Treatment Options in Small Cell Lung Cancer, and Selected Preclinical Candidates for Next Generation Combination Therapies. Liguori, NR., Lee, Y., Borges, W., et al.[2022]

Small cell lung cancer (SCLC) is highly aggressive and often relapses after initial treatment, leading to poor survival rates, highlighting the need for new therapeutic strategies.

Recent research has identified several molecular targets for SCLC, and new agents are being developed and tested in clinical trials to improve treatment outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies in small cell lung cancer: a review. Abidin, AZ., Garassino, MC., Califano, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05450965

Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small ... 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 ...

2. trialx.com trialx.com/clinical-trials/listings/280134/study-of-plk1-inhibitor-onvansertib-in-relapsed-small-cell-lung-cancer/

Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small ... This phase II clinical trial will study the safety and efficacy of onvansertib to treat patients with small cell lung cancer (SCLC) who have ...

3. investors.cardiffoncology.com investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-data-ongoing-randomized

Cardiff Oncology Announces Positive Data from Ongoing ... Trial demonstrates 49% confirmed ORR in the 30mg onvansertib dose arm versus 30% confirmed ORR in the control arm in intent-to-treat ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40782437/

Single-cell transcriptomic and pharmacological studies of ... Onvansertib is currently under Phase II investigation to evaluate its safety and efficacy in patients with relapsed small cell lung cancer (SCLC) ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-08789

Testing the Effect of an Anticancer Drug, Onvansertib, in ... This phase II study evaluates the safety and effectiveness of onvansertib for the treatment of patients with small cell lung cancer.

6. investors.cardiffoncology.com investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-clinical-data-pancreatic

Release Details In small cell lung cancer, we are encouraged to observe single-agent activity with onvansertib monotherapy in this difficult-to-treat extensive ...