Nivolumab +/- Ipilimumab for Lung Cancer

Not currently recruiting at 1229 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Hepatitis, HIV, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for individuals with stage IV squamous cell lung cancer that has returned after treatment. Researchers compare two options: using nivolumab (an immune checkpoint inhibitor) alone or combining it with ipilimumab (another immune checkpoint inhibitor) to determine which is more effective at shrinking tumors. This trial targets those who have not previously received certain immune-targeting drugs and do not have active autoimmune diseases. Individuals with recurrent lung cancer who have not tried these specific treatments may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, providing access to potentially effective treatments.

Do I have to stop taking my current medications for this trial?

The trial requires that you have not taken certain immune-related medications recently, like corticosteroids above a certain dose, within 14 days before joining. However, it doesn't specify if you need to stop other medications, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of nivolumab and ipilimumab is generally well-tolerated, though some risks exist. One study found serious side effects in about 1.6% of patients, including lung problems like pneumonitis, which is inflammation of the lung tissue. Another study reported that 7% of patients experienced immune-related lung issues.

For nivolumab alone, safety aligns with findings from other studies. Severe side effects occurred in about 3.6% of patients, including infections such as sepsis. Overall, while both treatments carry some risks, past research considers them manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nivolumab and ipilimumab for lung cancer because they work differently from traditional treatments like chemotherapy and radiation. Unlike these standard therapies, which directly attack cancer cells, nivolumab and ipilimumab harness the power of the immune system. Nivolumab blocks the PD-1 pathway, helping the immune system recognize and attack cancer cells, while ipilimumab targets CTLA-4 to boost immune response further. This dual-action approach has the potential to offer a more targeted attack on cancer cells, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that using nivolumab and ipilimumab together holds promise for treating advanced non-small-cell lung cancer (NSCLC). In this trial, some participants will receive this combination, which studies have found can greatly improve survival rates compared to traditional chemotherapy. One study showed that this treatment more than tripled the survival rate over six years for some patients. Other participants in this trial will receive nivolumab alone, and studies have shown that about 42% of patients with advanced squamous NSCLC were still alive after treatment. These treatments enhance the body's immune system to fight cancer cells more effectively. ^{2 4 6 7 8}

Who Is on the Research Team?

Vassiliki Papadimitrakopoulou

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for patients with stage IV squamous cell lung cancer that has returned after treatment. Participants must not have allergies to nivolumab or ipilimumab, no recent steroids or immunosuppressants, no HIV/AIDS, and should be free of certain heart conditions. They can't have had prior treatments targeting immune checkpoints and must not suffer from active autoimmune diseases.

Inclusion Criteria

I do not have lung disease that causes symptoms or could affect lung toxicity treatment.

Patients who can complete Patient Reported Outcomes (PRO) forms in English are required to complete a pre-study S1400I Patient Reported Outcomes (PRO) Questionnaire and a pre-study S1400I European Quality of Life Five Dimension (EQ-5D) Questionnaire within 14 days prior to registration; NOTE: Patients enrolled to S1400I prior to 9/1/2016 are not eligible for the PRO study

I have not received treatments targeting immune checkpoints.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab with or without ipilimumab intravenously. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 1 year, then every 6 months for up to 3 years.

Up to 3 years

Every 3 months for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study compares the effectiveness of two monoclonal antibodies: nivolumab alone versus nivolumab combined with ipilimumab in treating recurrent lung cancer. It's a phase III trial for those who didn't qualify for other biomarker-driven studies.

How Is the Trial Designed?

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

Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 60 minutes on day 1 of every third course (every 42 days). Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (nivolumab) Active Control 4 Interventions

Patients receive nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

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

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 Updated results presented in abstract form reported prolonged survival with a median of 9.2–14.9 months across the cohorts with a 1-year survival of 32–56% and ...

4. 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 ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2202170

Neoadjuvant Nivolumab plus Chemotherapy in Resectable ... Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable ...

6. 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, ...

7. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results Access OPDIVO® clinical trial results for your cancer type. Please see Indication and Important Safety Information ... lung cancer (called non-small cell lung ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01503

Five-Year Survival Outcomes With Nivolumab Plus ... Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a 5-year survival rate of only 7%, but more recently, immune ...