Evolocumab + Immunotherapy for Lung Cancer

(TOP2101 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Scott Antonia, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Scott Antonia

Must not be taking: PCSK9 inhibitors, Steroids

Disqualifiers: Active TB, Hepatitis B/C, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a research study to find out the safety and tolerability of combining the drug evolucumab with standard immunotherapy in people with advanced lung cancer (a type called non-small cell lung cancer). Nivolumab (Opdivo™) and ipilimumab (Yervoy™) are immunotherapy-type drugs which are approved for the treatment of advanced lung cancer that has expression of PD-L1 greater than or equal to 1%. Evolucumab is being combined with nivolumab and ipilimumab to see if it will improve the anti-tumor capabilities of the immunotherapy. Adding evolocumab to the combination of nivolumab and ipilimumab has not been tested in people before and is considered investigational.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain therapies like systemic steroids or other immunosuppressive treatments within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Evolocumab, Repatha, Ipilimumab, Yervoy, Nivolumab, Opdivo for lung cancer?

Research shows that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) is effective in treating advanced non-small cell lung cancer (NSCLC), improving survival compared to chemotherapy. This combination has shown durable and long-term benefits, especially in patients with certain tumor characteristics. ^{1 2 3 4 5}

Is the combination of Evolocumab and immunotherapy safe for humans?

The combination of nivolumab and ipilimumab, which are types of immunotherapy, has been studied in patients with lung cancer and generally shows a manageable safety profile. Some side effects are related to the immune system, like inflammation of the pituitary gland, intestines, and thyroid, but these can often be managed with medication. ^{3 5 6 7 8}

What makes the drug combination of Evolocumab, Ipilimumab, and Nivolumab unique for lung cancer treatment?

The combination of Ipilimumab and Nivolumab is unique because it uses two immune checkpoint inhibitors to enhance the body's immune response against lung cancer, offering a chemotherapy-free option for patients with advanced non-small cell lung cancer (NSCLC). This approach has shown durable and long-term efficacy compared to traditional chemotherapy. ^{1 3 9 10 11}

Eligibility Criteria

This trial is for adults over 18 with advanced non-small cell lung cancer (NSCLC) who haven't had chemotherapy, radiation, or biologic therapy for their current metastatic condition. They should have a performance status indicating they can carry out daily activities with little to no assistance and must not have other active cancers or serious autoimmune diseases.

Inclusion Criteria

I do not have an autoimmune disease that prevents me from taking nivolumab.

Signed written informed consent including HIPAA according to institutional guidelines.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You don't have a place where the doctor can take a small sample of tissue for testing before starting treatment.

I have a history of active tuberculosis.

My brain metastases are treated and controlled without high dose steroids.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks, with or without evolocumab 140 mg SC every 2 weeks

4 weeks

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Evolocumab (Monoclonal Antibodies)
• Ipilimumab (Monoclonal Antibodies)
• Nivolumab (Monoclonal Antibodies)

Trial Overview The study tests the combination of Evolocumab with standard immunotherapy drugs Nivolumab and Ipilimumab in treatment-naïve patients. It aims to determine if this new mix can enhance the immune system's ability to fight lung tumors more effectively than existing treatments.

Participant Groups

Group I: ipilimumab/nivolumab/evolucumab Experimental Treatment 3 Interventions

Subjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks plus evolocumab 140 mg SC every 2 weeks

Group II: Ipilimumab/nivolumab Active Control 2 Interventions

Subjects receive ipilimumab 1 mg/kg IV every 6 weeks and nivolumab 240 mg IV every 2 weeks.

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

🇺🇸 Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

🇪🇺 Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Duke Univ. Medical Center Durham, NC

Who Is Running the Clinical Trial?

Scott Antonia Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021] Frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy) induced durable and long-term efficacy, compared with chemotherapy, in patients with advanced non-small cell lung cancer (NSCLC) and tumor PD-L1 expression greater than 1% or less than 1%, according to updated results from part 1 of the phase 3 CheckMate 227 (NCT02477826)trial presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

2. England pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023] First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.

3. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. [2022] Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC.

4. United States pubmed.ncbi.nlm.nih.gov

High TMB Predicts Immunotherapy Benefit. [2019] The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden. After 1 year, progression-free survival was 43% for patients treated with the checkpoint inhibitor combination, compared with 13% for patients treated with chemotherapy.

5. England pubmed.ncbi.nlm.nih.gov

Ipilimumab: its potential in non-small cell lung cancer. [2021] Ipilimumab is a fully human monoclonal antibody that enhances antitumor immunity by way of cytotoxic T-lymphocyte antigen 4 blockade. It has already been approved by the US Food and Drug Administration for the treatment of metastatic melanoma and is being investigated for treating other solid tumors such as renal cell, prostate and lung cancers. This review details the potential of ipilimumab in the management of non-small cell lung cancer (NSCLC). In particular, ipilimumab showed promising results in a first-line NSCLC phase II study combining carboplatin/paclitaxel chemotherapy with concurrent or phased ipilimumab. The median immune-related progression-free survival was 5.68 months for the phased ipilimumab arm versus 4.63 months for chemotherapy alone (hazard ratio [HR] = 0.68, p = 0.026) and 5.52 months for the concurrent ipilimumab arm versus 4.63 months for chemotherapy alone (HR = 0.77, p = 0.094). The main adverse events were immune related, such as hypophysitis, enterocolitis, and hyperthyroidism. These adverse events may be improved with high-dose glucocorticoids and may be correlated with tumor response. Phase III studies are ongoing. Future studies may investigate ipilimumab in the management of early stage lung cancer. Strategies for potential translational research studies are also discussed to identify prognostic and predictive biomarkers for the use of ipilimumab in the treatment of patients with NSCLC.

6. United States pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023] We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and efficacy outcomes after NIVO+IPI discontinuation owing to treatment-related adverse events (TRAEs).

7. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022] Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or

8. Switzerland pubmed.ncbi.nlm.nih.gov

Focus on Nivolumab in NSCLC. [2021] Immunotherapy is changing the treatment of non-small cell lung cancer (NSCLC). The PD-1 inhibitor nivolumab has demonstrated meaningful results in terms of efficacy with a good safety profile. The novel approach to treating NSCLC using immunotherapy still has unsolved questions and challenging issues. The main doubts regarding the optimal selection of the patient are the role of this drug in first line of treatment, the individualization of the correct methodology of radiologic assessment and efficacy analysis, the best management of immune-mediated adverse events, and how to overcome the immunoresistance. The aim of this review is to analyze literature data on nivolumab in lung cancer with a focus on critical aspects related to the drug in terms of safety, the use in clinical practice, and possible placement in the treatment algorithm.

9. Switzerland pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. [2020] Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

10. United States pubmed.ncbi.nlm.nih.gov

Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. [2022] Ipilimumab is an antibody that targets the cytotoxic T-lymphocyte antigen-4 to potentiate an antitumor response. Adding ipilimumab 10 mg/kg to paclitaxel (PTX) and carboplatin (CBDCA) in a phased schedule improved progression-free survival in a phase II non-small-cell lung cancer (NSCLC) study.

11. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. [2019] Nivolumab and ipilimumab, two therapeutic immune checkpoint inhibitor antibodies that block PD-1 and CTLA-4, respectively, have indications in cancer as single agents and in combination. In this Review, we examine the potential role of dual immune checkpoint inhibition with nivolumab plus ipilimumab in the management of patients with previously untreated advanced non-small-cell lung cancer, based on results from the Phase III CheckMate 227 study. Immunotherapies with indications in the first-line treatment of non-small-cell lung cancer include pembrolizumab alone and combined with chemotherapy, and atezolizumab combined with bevacizumab and chemotherapy. CheckMate 227 is the first Phase III study evaluating first-line chemotherapy-sparing combination immunotherapy and including tumor mutational burden as a biomarker for patient selection.