Immunotherapy for Lung Cancer

(NA_00092076 Trial)

Not currently recruiting at 6 trial locations

Overseen By Patrick Forde, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Active infections, Brain metastasis, 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

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs, including Nivolumab and Ipilimumab (both immunotherapy drugs), to determine their safety and effectiveness for certain types of lung cancer. It focuses on high-risk non-small-cell lung cancer (NSCLC) that can still be surgically removed. The study compares different treatments to assess their impact on the immune system and to inform future trials. Individuals with NSCLC diagnosed through a core biopsy and deemed suitable for surgery might be a good fit for this trial. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drugs.

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

Research has shown that the treatments in this clinical trial have promising safety records from previous studies.

For nivolumab, studies indicate a safety profile similar to that observed in other trials, with serious side effects in about 3.6% of patients. Common side effects might include tiredness, skin rash, or diarrhea, but these are usually manageable.

When combined with ipilimumab, nivolumab has been successfully used in patients with advanced non-small-cell lung cancer (NSCLC). Real-world data suggests this combination is as safe as other similar treatments. Patients have experienced long-term benefits with generally well-tolerated side effects.

Studies have also shown that the combination of nivolumab with carboplatin and paclitaxel is safe. Patients handled this mix well, with no new or unexpected safety issues.

These findings suggest that the treatments in this trial are generally well-tolerated. However, anyone considering joining the trial should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they combine innovative immunotherapy approaches that differ from traditional chemotherapy options like cisplatin and gemcitabine. Nivolumab and Ipilimumab, for example, are checkpoint inhibitors that enhance the immune system's ability to fight cancer by targeting and blocking proteins that prevent immune cells from attacking tumors. This is a departure from standard treatments that directly target the cancer cells themselves. Additionally, the combination of Nivolumab with Carboplatin and Paclitaxel offers a more comprehensive attack on the cancer by integrating immunotherapy with chemotherapy, potentially improving outcomes and reducing the tumor size before surgery. These distinct mechanisms and combinations present promising new ways to enhance treatment effectiveness and patient outcomes in lung cancer therapy.

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

This trial will compare different immunotherapy approaches for lung cancer. Studies have shown that using nivolumab and ipilimumab together, one of the treatment arms in this trial, can extend survival in people with non-small-cell lung cancer (NSCLC) compared to chemotherapy alone. This combination works well as an initial treatment for advanced stages of the disease. Another arm in this trial involves nivolumab alone, which research indicates can improve survival rates and has fewer side effects than some chemotherapy drugs. Additionally, this trial includes an arm combining nivolumab with carboplatin and paclitaxel, which has shown promising results in delaying disease progression. These findings suggest these treatments could be effective options for those with high-risk resectable NSCLC. ^{2 4 5 6 7}

Who Is on the Research Team?

Patrick Forde, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for adults with high-risk resectable non-small cell lung cancer (NSCLC), who have good organ function and performance status. They must not be incarcerated, pregnant, or have other serious health issues like active infections or autoimmune diseases. Participants need to agree to use contraception and provide tissue samples for research.

Inclusion Criteria

My lung cancer diagnosis was confirmed with a core biopsy.

I am fully active or can carry out light work.

Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at SKCCC or MSKCC

Exclusion Criteria

History of allergy to study drug components

I have tested positive for HIV/AIDS.

I have received cancer treatment before surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Preoperative administration of nivolumab +/- ipilimumab or nivolumab with carboplatin and paclitaxel

6 weeks

3 cycles every 21 days

Surgery

Planned surgery following neoadjuvant treatment

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nivolumab
• Nivolumab and Ipilimumab
• Paclitaxel

Trial Overview The study tests the safety of giving Nivolumab alone or with Ipilimumab before surgery in NSCLC patients. It also looks at how these drugs affect immune cells in tumors and blood. The goal is to inform future trials on immunotherapies for both early-stage and advanced lung cancer.

How Is the Trial Designed?

Group I: Arm C- Nivolumab, Carboplatin, & Paclitaxel Experimental Treatment 3 Interventions

Nivolumab 360 mg IV, Carboplatin AUC 5 or 6 IV, and Paclitaxel 175 or 200 mg/m2 IV every 21 days for 3 cycles prior to planned surgery on Day 0.

Group II: Arm B- Nivolumab Experimental Treatment 1 Intervention

Nivolumab administration: Three doses of nivolumab will be administered to enrolled patients on Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.

Group III: Arm A- Nivolumab and Ipilimumab Experimental Treatment 2 Interventions

One dose of Nivolumab 3mg/kg IV \& Ipilimumab 1mg/kg will be administered to enrolled patients on Day-42, then 2 doses of Nivolumab 3mg/kg will be administered to enrolled patients on Day-28 and Day-14

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

In a phase II study involving 155 patients with advanced non-small-cell lung cancer, the combination of paclitaxel and carboplatin resulted in a 34% objective response rate, indicating significant efficacy in treating this cancer type.

The treatment was generally safe, with manageable side effects like leukopenia and peripheral neuropathy, and a median survival of 8 months, along with a 1-year survival rate of 42%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. Greco, FA., Hainsworth, JD.[2015]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

In a study of 956 patients with advanced squamous non-small-cell lung cancer (NSCLC), the addition of ipilimumab to standard chemotherapy did not significantly improve overall survival compared to chemotherapy alone, with median survival times of 13.4 months versus 12.4 months, respectively.

The combination of ipilimumab and chemotherapy was associated with higher rates of severe treatment-related adverse events, including 51% experiencing grade 3 or 4 events, compared to 35% with chemotherapy plus placebo, indicating a need for careful consideration of safety in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer. Govindan, R., Szczesna, A., Ahn, MJ., et al.[2022]

The combination of paclitaxel and carboplatin has shown promising results in treating advanced non-small-cell lung cancer (NSCLC), with reported 1-year survival rates as high as 54%, making it a widely used regimen in clinical practice.

This combination therapy has been effective without additional toxicity, allowing for full doses of both drugs to be administered, and is currently being evaluated in ongoing studies for earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer. Belani, CP.[2015]

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]

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]

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

Immunotherapy is becoming a key part of first-line treatment for non-small cell lung cancer (NSCLC), with various phase 3 studies showing the effectiveness of drugs targeting PD-1, PD-L1, and CTLA-4, often in combination with chemotherapy.

Patients with high PD-L1 expression (≥ 50%) can be treated with single-agent Pembrolizumab or Atezolizumab, while those with lower expression have multiple treatment options, including combinations of immunotherapy and chemotherapy, highlighting the tailored approach based on tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. Nasser, NJ., Gorenberg, M., Agbarya, A.[2020]

In a study of 33 patients with progressive or recurrent non-small cell lung cancer (NSCLC) who had previously undergone platinum-based chemotherapy, Abraxane showed a partial response rate of 33.3%, with better outcomes in patients with squamous cell carcinoma (41.7% response) compared to those with adenocarcinoma (21.1%).

The treatment demonstrated a disease control rate of 75.8% and a median progression-free survival of five months, with manageable side effects, indicating that Abraxane is a potentially effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Abraxane in treatment of progressive and recurrent non-small cell lung cancer patients: A retrospective clinical study. Yuan, DM., Lv, YL., Yao, YW., et al.[2019]

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

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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 ...

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