Nivolumab + Chemotherapy +/- Radiation for Lung Cancer

(CA209-6K6 Trial)

Overseen by Brendon Stiles, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Montefiore Medical Center

Must not be taking: Immunosuppressants, Immunotherapy

Disqualifiers: Other malignancy, Autoimmune disorders, others

Stay on Your Current Meds

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of nivolumab, chemotherapy, and sometimes targeted radiation in patients with a specific type of lung cancer that can be surgically removed. The treatment aims to shrink the tumor and kill cancer cells, making surgery more effective. Nivolumab with chemotherapy has been approved by the FDA as the first immunotherapy-based treatment for non-small cell lung cancer.

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 use immunosuppressive medications within 14 days before starting the trial, except for certain low-dose steroids and specific premedications.

What data supports the effectiveness of the treatment Nivolumab + Chemotherapy +/- Radiation for Lung Cancer?

Research shows that platinum-based chemotherapy, like oxaliplatin, is effective for advanced lung cancer, and nivolumab, an immunotherapy drug, can improve survival in lung cancer patients. Combining these treatments may enhance effectiveness, although it could increase side effects. ^{1 2 3 4 5}

Is the combination of Nivolumab and platinum-based chemotherapy safe for lung cancer patients?

Nivolumab combined with platinum-based chemotherapy, like oxaliplatin, has been studied for lung cancer and is generally considered safe, though it may increase side effects. Oxaliplatin is often preferred for patients who cannot tolerate other platinum-based treatments due to its more favorable side effect profile. ^{2 3 4 5 6}

How is the drug Nivolumab with chemotherapy and radiation unique for lung cancer treatment?

Nivolumab, when used as a first-line treatment for non-small cell lung cancer, can improve survival rates, and its combination with platinum-based chemotherapy and radiation therapy offers a novel approach by potentially enhancing the immune response against cancer cells. However, adding chemotherapy may increase the treatment's side effects. ^{1 3 7 8 9}

Research Team

Brendon Stiles, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

Adults over 18 with resectable stage IIA to IIIB non-small cell lung cancer, who haven't had previous lung cancer treatment. They must be able to undergo radiation therapy if needed, have a good performance status (ECOG 0 or 1), and agree to use effective birth control. Excluded are those on recent immunosuppressants, with certain allergies or autoimmune diseases, active infections like TB or hepatitis B/C, pregnant/breastfeeding women, and anyone with another primary malignancy.

Inclusion Criteria

I am fully active or can carry out light work.

My lung cancer is at a specific stage and I am eligible for surgery aimed at curing it.

I am older than 18 years.

Exclusion Criteria

I do not have active infections like TB, hepatitis B, or hepatitis C.

I haven't taken strong immune system suppressing drugs in the last 14 days, except for minor exceptions like creams or low-dose steroids.

I have had an autoimmune or inflammatory disorder but no active diverticulitis in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant nivolumab and platinum-based doublet chemotherapy for 3 cycles, with or without sub-ablative stereotactic body radiation therapy

9 weeks

3 visits (in-person) every 3 weeks

Surgical Resection

Surgical resection of the primary tumor and lymph nodes following neoadjuvant therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pathological response and survival outcomes

12 months

Treatment Details

Interventions

• Nivolumab (Checkpoint Inhibitor)
• Platinum Doublet (Chemotherapy)
• Sub-ablative Stereotactic Body Radiation Therapy (Radiation)

Trial Overview This study is testing the effectiveness of Nivolumab (an immunotherapy drug) combined with chemotherapy before surgery in patients with early-stage non-small cell lung cancer. Some participants will also receive stereotactic body radiation therapy. The goal is to see if these treatments can improve outcomes when given before tumor removal.

Participant Groups

Group I: Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3) Experimental Treatment 3 Interventions

SBRT will be delivered near the conclusion of cycle 1 with platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. The intent is to deliver SBRT on three consecutive days when the concentration of radiosensitizing chemotherapy agents in the subject's system is at a minimum, to minimize toxicity risks. It is expected that some subjects may not receive SBRT on three consecutive days due to machine breakdown, inclement weather, or other logistic issues. Subjects must not receive SBRT within 72 hours after a cisplatin or carboplatin infusion

Group II: Nivolumab + Platinum Doublet Chemotherapy Active Control 2 Interventions

All participants will receive platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. Carboplatinum (AUC=5) can be used instead of Cisplatin (75 mg/m2) from cycle 2 for Cisplatin induced neuro/oto/nephrotoxicity as long as the subject remains eligible for doublet chemotherapy. Participants with nonsquamous tumors will receive pemetrexed (500 mg/m2). Participants with squamous tumors will receive either docetaxel (75 mg/m2 on day 1) or gemcitabine (1000 mg/m2 on days 1, 8). Cycles will be every 3 weeks and a maximum of a 2 week delay will be permitted for resolution of toxicities.

Nivolumab is already approved in Canada, Switzerland for the following indications:

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Andrew D. Racine

Montefiore Medical Center

Chief Medical Officer since 1992

MD, PhD from New York University; Undergraduate degree from Harvard University

Philip O. Ozuah

Montefiore Medical Center

Chief Executive Officer since 2019

MD, PhD from New York University

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

Findings from Research

Cisplatin combined with either a vinca alkaloid or etoposide is highly effective in reducing mortality for patients with non-small cell lung cancer, as shown in meta-analyses comparing chemotherapy to supportive care.

Recent studies indicate that combining cisplatin-based chemotherapy with new agents and radiotherapy can significantly prolong survival and improve outcomes for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. Shinkai, T., Saijo, N.[2018]

In a phase II study involving 29 patients with advanced non-small-cell lung cancer (NSCLC), the combination of oxaliplatin and docetaxel showed an overall response rate of 37%, indicating its potential efficacy as a treatment option.

The treatment was well tolerated, with no unusual adverse events reported; the most common severe side effects were anemia (14%) and hyperglycemia (10%), suggesting a manageable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). Raez, LE., Santos, ES., Lopes, G., et al.[2018]

Nivolumab, used as a first-line treatment for non-small cell lung cancer, shows promise in improving patient survival rates.

Combining nivolumab with platinum-doublet chemotherapy did not enhance survival benefits and may increase toxicity, indicating a need for careful consideration when using these treatments together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab May Work as First-Line NSCLC Therapy. [2018]

In a phase II trial involving 33 patients with stage IV non-small cell lung cancer (NSCLC), the combination of oxaliplatin and docetaxel resulted in an objective response rate of 33.3%, indicating that this treatment can be effective for some patients.

The median progression-free survival was 3.6 months and median overall survival was 10.9 months, with the most common side effect being grade 3-4 neutropenia occurring in 51.5% of patients, suggesting that while the treatment is effective, it does come with significant hematologic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of docetaxel plus oxaliplatin as a first-line chemotherapy in patients with advanced or metastatic non-small cell lung cancer. Ban, H., Kim, KS., Oh, IJ., et al.[2018]

Oxaliplatin, a third-generation platinum analogue, shows similar clinical activity to standard platinum doublets like cisplatin and carboplatin in treating advanced non-small-cell lung cancer (NSCLC), with response rates ranging from 23% to 48% and median overall survival between 7.3 to 13.7 months.

The toxicity profile of oxaliplatin is generally more favorable compared to cisplatin, making it a suitable alternative for patients who cannot tolerate cisplatin, although further randomized phase III trials are necessary to identify specific patient groups that may benefit most from oxaliplatin-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin in first-line therapy for advanced non-small-cell lung cancer. Raez, LE., Kobina, S., Santos, ES.[2020]

A meta-analysis of 8 studies with 1047 patients found that oxaliplatin-based doublets have similar efficacy to carboplatin/cisplatin doublets in treating nonsmall cell lung cancer, with comparable overall survival and disease control rates.

Oxaliplatin doublets resulted in significantly less severe leukocytopenia and neutropenia compared to carboplatin/cisplatin, suggesting a more favorable toxicity profile, making oxaliplatin a viable alternative for patients who cannot tolerate traditional platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer. Yu, J., Xiao, J., Yang, Y., et al.[2022]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase 3 clinical trial involving 252 patients with advanced squamous non-small cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone, with median survival times of 10 months and 11 months respectively.

While the combination treatment showed a slightly better progression-free survival (IA-PFS) of 3.8 months compared to 2.9 months for nivolumab alone, the difference was not statistically significant, and both treatments had similar response rates and adverse event profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. Gettinger, SN., Redman, MW., Bazhenova, L., et al.[2022]

In a phase II clinical trial involving 40 patients with locally advanced non-small-cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and radiation therapy resulted in a high overall response rate of 75.7% and a median overall survival of 20.5 months.

While the treatment was effective, it also led to significant toxicity, with 46% of patients experiencing grade 3 or 4 esophagitis, although late esophageal complications were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. Choy, H., Akerley, W., Safran, H., et al.[2017]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). [2018]

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

Nivolumab May Work as First-Line NSCLC Therapy. [2018]

4. Singapore pubmed.ncbi.nlm.nih.gov

Efficacy and safety of docetaxel plus oxaliplatin as a first-line chemotherapy in patients with advanced or metastatic non-small cell lung cancer. [2018]

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

Oxaliplatin in first-line therapy for advanced non-small-cell lung cancer. [2020]

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

Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer. [2022]

7. China pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. [2010]

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

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. [2022]

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

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. [2017]