What is the mechanism of action of this treatment?

The most common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy, radiotherapy, and immunotherapy. Chemotherapy, often using drugs like etoposide and cisplatin, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Radiotherapy uses high-energy radiation to kill cancer cells and shrink tumors. Immunotherapy, such as anti-PD-1 or anti-PD-L1 therapies, enhances the body's immune response against cancer cells. These treatments are crucial for SCLC patients due to the aggressive nature of the disease and its tendency to spread quickly. Additionally, PLK-1 inhibitors like Onvansertib target the polo-like kinase 1 enzyme, which is involved in cell division and is overexpressed in many cancers, including SCLC. By inhibiting PLK-1, these drugs can disrupt cancer cell proliferation and induce apoptosis, offering a potential new avenue for treatment.

What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy regimens such as etoposide with cisplatin or carboplatin, and newer approaches like immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 therapies). Known side effects of these treatments can include nausea, vomiting, hair loss, fatigue, increased risk of infection, and low blood cell counts. Immune checkpoint inhibitors may also cause immune-related adverse events such as pneumonitis, colitis, hepatitis, and endocrinopathies. For PLK-1 inhibitors like Onvansertib, potential side effects could include gastrointestinal disturbances, hematologic toxicities, and fatigue, although specific data on Onvansertib's side effects are not detailed in the provided context.

What prior FDA approvals exist?

The FDA has approved several treatments for Small Cell Lung Cancer (SCLC), primarily focusing on chemotherapy regimens. Commonly approved drugs include etoposide combined with either cisplatin or carboplatin. Additionally, immune checkpoint inhibitors such as nivolumab (anti-PD-1) have been approved for use in SCLC. While Onvansertib, a PLK-1 inhibitor, is currently being studied in a phase II trial, there is no specific mention of prior FDA approvals for PLK-1 inhibitors in the treatment of SCLC.

What other types of research exist?

Promising novel alternatives to Onvansertib for SCLC patients include immune checkpoint inhibitors such as nivolumab and pembrolizumab, which have shown efficacy in various solid tumors including SCLC. Additionally, targeted therapies like entrectinib, which inhibits NTRK1-3 and ROS1, may offer potential benefits for patients with specific genetic alterations. These therapies are being actively studied and have shown encouraging results in clinical trials.

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PLK-1 Inhibitor

Onvansertib for Small Cell Lung Cancer

Phase 2

Recruiting

Led By Taofeek Owonikoko, MD, PhD

Research Sponsored by Taofeek Owonikoko

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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

Must not have

Patients with active GI disorders likely to impair the absorption of oral medications

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing onvansertib, a drug that blocks an enzyme helping cancer cells grow, in patients with small cell lung cancer who can't use standard chemotherapy. By stopping the cancer cells from repairing themselves, the drug aims to slow down or stop their growth.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include allergic reactions similar to those from drugs like Onvansertib; however specific side effects are not listed as data on adverse events are currently unavailable. Patients' normal organ function must be confirmed before starting treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am over 18 years old.

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

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My lung cancer diagnosis was confirmed through lab tests.

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I can take care of myself but might not be able to do heavy physical work.

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My organ and bone marrow functions are normal.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a stomach or intestine problem that affects how I absorb pills.

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I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

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

Overall survival (OS)

Progression-free survival (PFS)

Side effects data

From 2021 Phase 1 & 2 trial • 72 Patients • NCT03303339

38%

Febrile neutropenia

31%

Hypokalaemia

28%

Diarrhoea

28%

Stomatitis

25%

Fatigue

22%

Nausea

22%

Epistaxis

19%

Oedema peripheral

19%

Platelet count decreased

19%

Alopecia

16%

Hypophosphataemia

16%

Acute myeloid leukaemia

16%

Sepsis

16%

Dyspnoea

16%

Cough

16%

Hypoalbuminaemia

13%

Hypoxia

13%

Lung infection

13%

Anaemia

13%

Rash maculo-papular

13%

Rash

13%

Hypocalcaemia

13%

Arthralgia

13%

Hypertension

13%

Hypotension

Electrocardiogram QT prolonged

Syncope

Pneumonia

Cellulitis

Headache

Abdominal pain upper

Oral pain

Staphylococcal infection

Urinary tract infection

Hypomagnesaemia

Dizziness

Oropharyngeal pain

Petechiae

Decreased appetite

Alanine aminotransferase increased

Abdominal pain

Escherichia bacteraemia

Blood creatine increased

Mucosal inflammation

Hyperbilirubinaemia

Pleural effusion

Vomiting

Fluid overload

Ear pain

Lower gastrointestinal haemorrhage

Dry mouth

Dry skin

Oral candidiasis

Neuropathy peripheral

Fall

Pyrexia

Nasal congestion

Ecchymosis

Blood alkaline phosphatase

Insomnia

Pain in extremity

Haematemesis

Odynophagia

Proctalgia

Staphylococcal bacteraemia

Bacteraemia

Pneumonia fungal

Pruritus

Dermatitis contact

Purpora

Non-cardiac chest pain

Hyperkalaemia

Hypercalcaemia

Flank pain

Aspartate aminotransferase increased

Neutrophil count decreased

Blood bilirubin increased

Pleuritic pain

Haematoma

Conjunctival haemorrhage

Myalgia

Back pain

Atrial fibrillation

Mallory-Weiss syndrome

Tumour lysis syndrome

Hyperglycaemia

Upper gastrointestinal haemorrhage

Pain

Respiratory failure

Rash pruritic

Musculoskeletal pain

Face oedema

Hyponatraemia

Contusion

Septic shock

Candida infection

Granulicatella bacteraemia

Kidney infection

Pancytopenia

Colitis

Melaena

Constipation

Transfusion reaction

Dysgeusia

Dyspnoea exertional

Wheezing

Neutropenia

Weight decreased

Anxiety

Eye pruritus

White blood cell count decreased

Neutropenic colitis

Mental status changes

Chills

Sinus tachycardia

Haemoptysis

Aphasia

100%

80%

60%

40%

20%

Study treatment Arm

Phase 2: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 90 mg/m^2 + Decitabine

Phase 1b: Onvansertib 12 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 40 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 60 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 12 mg/m^2 + Decitabine

Phase 1b: Onvansertib 40 mg/m^2 + Decitabine

Phase 1b: Onvansertib 60 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Low-dose Cytarabine

Phase 1b: Onvansertib 18 mg/m^2 + Decitabine

Phase 1b: Onvansertib 27 mg/m^2 + Decitabine

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single Treatment ArmExperimental Treatment1 Intervention

Onvansertib

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Onvansertib

Not yet FDA approved

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy, radiotherapy, and immunotherapy. Chemotherapy, often using drugs like etoposide and cisplatin, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Radiotherapy uses high-energy radiation to kill cancer cells and shrink tumors. Immunotherapy, such as anti-PD-1 or anti-PD-L1 therapies, enhances the body's immune response against cancer cells. These treatments are crucial for SCLC patients due to the aggressive nature of the disease and its tendency to spread quickly. Additionally, PLK-1 inhibitors like Onvansertib target the polo-like kinase 1 enzyme, which is involved in cell division and is overexpressed in many cancers, including SCLC. By inhibiting PLK-1, these drugs can disrupt cancer cell proliferation and induce apoptosis, offering a potential new avenue for treatment.

Caspase-9b Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-κB and Lung Tumorigenesis.Overcoming resistance to tyrosine kinase inhibitors in renal cell carcinoma.Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung.