Nivolumab for Non-Small Cell Lung Cancer

(ANVIL Trial)

Not currently recruiting at 1045 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Pregnancy, Active infection, Autoimmune disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of nivolumab, an immunotherapy drug, after surgery and chemotherapy in patients with certain types of non-small cell lung cancer. The researchers aim to determine if nivolumab can enhance the immune system's ability to attack cancer cells and prevent recurrence or spread. Participants who have undergone surgery to remove stage IB-IIIA lung cancer and completed chemotherapy may qualify. One group will receive nivolumab, while another will be monitored without additional treatment for comparison. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic corticosteroids (more than 10 mg of prednisone per day) or other immunosuppressive medications within 2 weeks of joining the trial.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that nivolumab is generally well-tolerated by patients with non-small cell lung cancer. Studies have found that its side effects in everyday use resemble those seen in clinical trials, indicating they are mostly manageable and expected. However, some patients experienced serious side effects. Fatal reactions occurred in about 3.6% of patients when nivolumab was used with chemotherapy. Serious side effects may include infections like sepsis, which occurred in 1% of cases. Overall, while risks exist with nivolumab, many patients handle it without severe problems. ^{1 2 3 4 5}

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

Nivolumab is unique because it harnesses the power of the immune system to fight non-small cell lung cancer. Unlike traditional chemotherapy that directly attacks cancer cells but can also harm healthy cells, nivolumab works by blocking a protein called PD-1. This enables the immune system's T-cells to better recognize and attack cancer cells. Researchers are excited about nivolumab because it has the potential for fewer side effects and can offer a more targeted approach, potentially leading to longer-lasting responses in patients.

What evidence suggests that nivolumab might be an effective treatment for non-small cell lung cancer?

Studies have shown that nivolumab can help treat non-small cell lung cancer (NSCLC). In earlier research, 42% of patients with advanced NSCLC who received nivolumab remained alive during follow-up. Real-world studies also support its effectiveness for patients who had previous treatments. In this trial, some participants will receive nivolumab, which boosts the immune system to attack cancer cells, potentially preventing the cancer from growing and spreading. This makes it a promising option for NSCLC treatment after surgery and chemotherapy. Other participants will be in the observation arm, monitored with imaging and follow-up assessments. ^{3 4 6 7 8}

Who Is on the Research Team?

Jamie E Chaft

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults who've had surgery for stage IB-IIIA non-small cell lung cancer and are done with any chemotherapy. They must not be pregnant, breastfeeding, or have certain viral infections. Their liver and kidney functions should be normal, they can't have autoimmune diseases except some like type I diabetes or controlled hypothyroidism, and no prior immune checkpoint inhibitor treatments.

Inclusion Criteria

You have not had allergic reactions to drugs similar to nivolumab.

I've had a chest CT scan within the last month showing no signs of disease spread.

I am fully active or can carry out light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab intravenously every 4 weeks for up to 1 year

12 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Follow-up at 6 weeks, every 3 months for 2 years, every 6 months for 2 years, then annually for 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview The trial is testing if nivolumab (an immunotherapy drug) given after surgery and chemotherapy can help treat non-small cell lung cancer by boosting the body's immune response to attack cancer cells. It involves monitoring through scans like CT and PET, blood tests, and collecting biospecimens.

How Is the Trial Designed?

Group I: Arm I (nivolumab) Experimental Treatment 5 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT throughout the trial and blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.

Group II: Arm II (observation) Active Control 5 Interventions

Patients are followed serially with CT and/or PET/CT imaging for up to 1 year and then during follow-up. Patients also undergo blood sample collection during screening and follow-up. Patients may undergo an ECHO as clinically indicated on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Monoclonal antibodies like nivolumab and pembrolizumab, which target PD-1, have shown a survival benefit and better tolerability compared to standard second-line chemotherapy in non-small cell lung cancer, as demonstrated in three phase III trials.

Patients receiving PD-1 inhibitors may experience unique immune-related adverse events that require early recognition and a multidisciplinary management approach, highlighting the need for ongoing education among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring and Management of Immune-Related Adverse Events Associated With Programmed Cell Death Protein-1 Axis Inhibitors in Lung Cancer. O'Kane, GM., Labbé, C., Doherty, MK., et al.[2018]

In a study of 79 pre-treated patients with advanced non-small cell lung cancer, nivolumab significantly prolonged progression-free survival, especially in patients who had a partial response to prior treatments.

The occurrence of skin rash during nivolumab treatment was associated with improved long-term survival, suggesting that this side effect may indicate a favorable response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Pleiotropic Effects of Nivolumab in Pretreated Advanced or Recurrent Non-small Cell Lung Cancer Cases. Akano, Y., Kuribayashi, K., Funaguchi, N., et al.[2020]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

Nivolumab, a PD-1 receptor inhibitor, shows an objective response rate of 18% and a 1-year overall survival rate of 45% in patients with advanced non-small-cell lung cancer, based on a meta-analysis of 20 studies involving 3404 patients.

The presence of PD-L1 expression in patients is associated with a better response to nivolumab, indicating that PD-L1 status can help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials. Zhao, B., Zhang, W., Yu, D., et al.[2019]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

In a study of patients with non-small cell lung cancer treated with nivolumab, those who experienced serious adverse events (grade ≥3) had significantly better overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to those without such events.

The findings suggest that while serious adverse events are typically concerning, they may be associated with a more favorable treatment response in patients receiving nivolumab, indicating a complex relationship between adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. Blazek, J., Hosek, P., Hrabcova, K., et al.[2023]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/nsclc

Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or ...

2. opdivo.com opdivo.com/nsclc/clinical-trial-results/advanced-previously-treated-immunotherapy

Clinical trial results for previously treated stage 4 recurrent ... 42% of patients given OPDIVO® (nivolumab) for advanced squamous NSCLC were alive. People ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4346216/

Nivolumab in NSCLC: latest evidence and clinical potential This review will discuss results from early phase studies of nivolumab in solid tumors including non-small cell lung cancer (NSCLC)

4. sciencedirect.com sciencedirect.com/science/article/pii/S152573042030231X

Real-World Effectiveness of Nivolumab Monotherapy After ... This study confirmed the effectiveness of nivolumab monotherapy for previously treated advanced NSCLC in real-world clinical practice.

5. jto.org jto.org/article/S1556-0864(24)02355-4/fulltext

Long-Term Survival Outcomes With First-Line Nivolumab ... In patients with squamous NSCLC, median OS was 16.2 versus 8.2 months with nivolumab plus ipilimumab with or without chemotherapy versus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7738788/

Real-World Safety and Efficacy of Nivolumab in Advanced ... There is a lack of real-world data on the safety and efficacy of nivolumab in patients with previously treated advanced non-small-cell lung cancer (NSCLC) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8586674/

Real‐world safety of nivolumab in patients with non‐small‐ ... The 12‐month survival rate was 40.7%. In conclusion, the safety profile of nivolumab in this postmarketing surveillance was similar to that in clinical trials, ...

8. news.bms.com news.bms.com/news/details/2022/Landmark-Five-Year-Data-from-Phase-3-CheckMate--227-Trial-Demonstrate-Long-Term-Durable-Survival-Outcomes-with-Opdivonivolumab-Plus-Yervoy-ipilimumab-in-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx

Landmark Five-Year Data from Phase 3 CheckMate -227 ... Opdivo plus Yervoy nearly doubled overall survival rate at five years compared to chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC)