Nivolumab + Ipilimumab for Lung Cancer

(ATLAS Trial)

Overseen By Adrian Sacher, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Immunosuppressants, others

Disqualifiers: Autoimmune disorders, HIV, Hepatitis, 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

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: 4

Duration: 12 weeks

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well two drugs, nivolumab and ipilimumab (known as Opdivo and Yervoy, respectively, and both types of immunotherapy), work together in treating non-small cell lung cancer that has spread. Researchers seek to determine if these drugs can shrink tumors and improve patient outcomes. The trial is recruiting participants with metastatic non-small cell lung cancer who have not received previous treatments and whose tumors have a PDL1 status below 50%. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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 have received any anticancer therapy within 21 days or palliative radiotherapy within 14 days before starting the study treatment. Also, you should not be using immunosuppressive medication within 14 days before the first dose.

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

Research shows that the combination of nivolumab and ipilimumab has been studied for treating advanced non-small cell lung cancer. These studies indicate that patients generally tolerate these drugs well.

Some people experienced side effects, with common ones being tiredness, skin rash, and diarrhea. However, many patients continued treatment after managing these effects.

The studies suggest that this drug combination can be a safer option than traditional chemotherapy for some patients. The extensive research on nivolumab and ipilimumab provides a strong indication of their safety. Anyone considering joining a trial should discuss potential side effects and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Ipilimumab for treating non-small cell lung cancer because it targets the immune system differently than standard chemotherapy. Most current treatments focus on directly killing cancer cells, but these drugs are immunotherapies that work by unleashing the body's immune system to recognize and destroy cancer cells. Nivolumab blocks a protein called PD-1, while Ipilimumab blocks another protein called CTLA-4, both of which help cancer hide from the immune system. Together, they can potentially lead to a more robust and lasting immune response against the cancer.

What evidence suggests that nivolumab and ipilimumab could be effective for non-small cell lung cancer?

Research shows that using the drugs nivolumab and ipilimumab together can effectively treat advanced lung cancer. In this trial, participants will receive nivolumab and ipilimumab intravenously. Studies have found that patients who start with these drugs live longer than those who receive traditional chemotherapy. Specifically, the number of patients living for five years or more has increased significantly. This treatment helps the immune system recognize and attack cancer cells. These findings suggest that nivolumab and ipilimumab could be promising options for people with advanced lung cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Adrian G. Sacher

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

Adults with metastatic non-small cell lung cancer, weighing at least 35 kg and expected to live more than 12 weeks. They must not have had prior treatments for this diagnosis or certain other cancers in the last two years, no major organ transplants, active infections like HIV or hepatitis, and no recent heart issues. Participants need functioning organs/marrow and cannot be on immunosuppressants.

Inclusion Criteria

I have not had any treatment for my current lung cancer diagnosis.

My lung cancer has returned or spread to other parts.

My lung cancer can be of any type.

Exclusion Criteria

I am not incarcerated and can consent and follow study procedures.

I haven't taken immunosuppressive drugs in the last 14 days, with some exceptions.

I've had to stop IV drug treatments more than once due to bad reactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab every 3 weeks and ipilimumab every 6 weeks, with cfDNA testing to guide potential chemotherapy intensification

12 weeks

4 visits (in-person) for nivolumab, 2 visits (in-person) for ipilimumab

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival

4 years

What Are the Treatments Tested in This Trial?

Interventions

• cfDNA blood test
• Ipilimumab, Nivolumab
• Platinum-based Chemotherapy

Trial Overview The trial is testing the effectiveness of nivolumab and ipilimumab drugs on metastatic non-small cell lung cancer. It also examines how a cfDNA blood test can help track tumor changes during treatment. Patients will not have received previous surgery, radiation, or chemotherapy for their current cancer diagnosis.

How Is the Trial Designed?

Group I: Non-Small cell Lung Cancer Experimental Treatment 4 Interventions

Nivolumab, intravenously (given by vein), once every 3 weeks Ipilimumab, intravenously (given by vein), once every 6 weeks Participants will have blood samples taken for cell free deoxyribonucleic acid (cfDNA) testing. If there is an increasing or stable tumor cfDNA, platinum-doublet chemotherapy will be given.

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

Approved in United States as Yervoy for:

• Melanoma
• Colorectal cancer
• Renal cell carcinoma
• Hepatocellular carcinoma
• Non-small cell lung cancer

Approved in United States as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma
• Gastric cancer
• Gastroesophageal junction cancer

Approved in European Union as Yervoy for:

• Melanoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in Canada as Yervoy for:

• Melanoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma

Approved in Japan as Yervoy for:

• Melanoma

Approved in Japan as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

The phase III CheckMate-227 trial indicates that the combination of ipilimumab and nivolumab significantly improves progression-free survival in non-small cell lung cancer patients with a high tumor mutation burden, with 43% of patients remaining progression-free after 1 year.

In contrast, only 13% of patients treated with chemotherapy experienced progression-free survival, highlighting the potential efficacy of the checkpoint inhibitor combination over traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High TMB Predicts Immunotherapy Benefit. [2019]

The combination of nivolumab and ipilimumab has shown promise as a first-line treatment for previously untreated advanced non-small-cell lung cancer, as demonstrated in the Phase III CheckMate 227 study.

This study is significant because it is the first to evaluate a chemotherapy-sparing approach using dual immune checkpoint inhibition, while also considering tumor mutational burden as a biomarker for selecting suitable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. Reck, M., Borghaei, H., O'Byrne, KJ.[2019]

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 phase 1 study involving 78 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab as first-line therapy demonstrated a tolerable safety profile with no treatment-related deaths and manageable adverse events, such as increased lipase and pneumonitis.

The treatment showed promising efficacy, with confirmed objective response rates of 47% in the ipilimumab every-12-weeks cohort and 38% in the every-6-weeks cohort, suggesting potential benefits over anti-PD-1 monotherapy and warranting further investigation in larger trials.

NCBI (Pubmed)

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. Hellmann, MD., Rizvi, NA., Goldman, JW., et al.[2022]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

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. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

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 plus ipilimumab (N+I) and nivolumab plus ipilimumab with chemotherapy (N+I+chemotherapy) improve overall survival and progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC), but both treatments are not cost-effective compared to chemotherapy alone, with high incremental cost-effectiveness ratios (ICERs) of $239,072 and $838,198 per quality-adjusted life year (QALY) respectively.

The cost-effectiveness analysis showed that N+I had a very low probability (2.6%) of being considered cost-effective at a willingness-to-pay threshold of $150,000 per QALY, indicating that while these treatments may improve survival, they come at a significant financial burden to the healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer. Yang, SC., Kunst, N., Gross, CP., 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 plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

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. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Efficacy ... Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non-small cell lung cancer in CheckMate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9937094/

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab ... Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a poor prognosis, with a 5-year survival rate of 7%. Programmed death (ligand) ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910231

Nivolumab plus Ipilimumab in Advanced Non–Small-Cell ... First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC.

4. opdivo.com opdivo.com/nsclc/clinical-trial-results/advanced-pd-l1-positive-immunotherapy-combination

Non-small cell lung cancer (NSCLC) See how OPDIVO® (nivolumab) + YERVOY® (ipilimumab) performed in a clinical trial as first-line treatment for adults with stage 4 or recurrent advanced ...

5. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Opdivo-Plus-Chemotherapy-as-the-First-and-Only-Neoadjuvant-Only-Immuno-Oncology-Therapy-to-Demonstrate-Statistically-Significant-and-Clinically-Meaningful-Overall-Survival-in-Resectable-Non-Small-Cell-Lung-Cancer/default.aspx

The final analysis of overall survival in the CheckMate OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non- ...

6. 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)