Nivolumab + Chemotherapy +/- Radiation for Lung Cancer

(CA209-6K6 Trial)

Recruiting at 1 trial location

Overseen By Brendon Stiles, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Montefiore Medical Center

Must not be taking: Immunosuppressants, Immunotherapy

Disqualifiers: Other malignancy, Autoimmune disorders, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 3

Duration: 9 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for individuals with surgically removable non-small cell lung cancer. Researchers are examining the effectiveness of nivolumab (Opdivo, an immunotherapy drug) combined with chemotherapy, with some participants also receiving precise radiation therapy. The goal is to determine if adding radiation improves outcomes before surgery. Suitable candidates have lung cancer stages IIA to IIIB and are eligible for surgery. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that combining nivolumab with platinum-doublet chemotherapy has been studied for safety in patients with resectable non-small cell lung cancer (NSCLC). One study found that serious side effects occurred in 30% of patients receiving this treatment, meaning about 3 out of every 10 people experienced significant side effects.

For the combination of nivolumab, platinum-doublet chemotherapy, and a type of targeted radiation therapy called sub-ablative stereotactic body radiation therapy (SBRT), specific safety data remains less clear. However, the approval of nivolumab and chemotherapy together indicates some level of established safety. Researchers are exploring whether adding SBRT introduces any new risks or benefits.

This trial is in an early phase, so researchers are still collecting safety information. Early trials usually focus on ensuring a treatment is safe and identifying any serious side effects. If considering participation, discussing potential risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine nivolumab, a powerful immunotherapy drug, with chemotherapy and potentially radiation, offering a fresh approach to treating lung cancer. Unlike traditional treatments that rely solely on chemotherapy, nivolumab works by activating the body's immune system to better recognize and attack cancer cells. Additionally, the trial explores the use of Stereotactic Body Radiation Therapy (SBRT) alongside chemotherapy and nivolumab, aiming to deliver targeted radiation with minimal toxicity. This combination could enhance treatment effectiveness and reduce side effects, which are significant improvements over existing protocols.

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

Research has shown that combining nivolumab with platinum-doublet chemotherapy can improve outcomes for people with non-small cell lung cancer. In this trial, one group of participants will receive this combination, which studies have demonstrated can help patients live longer and reduce the likelihood of cancer returning after surgery. Another group will receive the same combination with the addition of stereotactic body radiation therapy (SBRT), which aims to further limit cancer spread and enhance survival. SBRT, a type of focused radiation, precisely targets tumors. Together, these treatments have shown promise in increasing survival rates and reducing cancer recurrence in lung cancer patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Brendon Stiles, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Platinum Doublet
• Sub-ablative Stereotactic Body Radiation Therapy

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union 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 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+

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 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 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]

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 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]

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]

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]

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]

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]

Citations

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Shifting the paradigm for resectable NSCLC - Opdivo Surgical outcomes from the phase 3 CheckMate 816 trial: nivolumab + platinum-doublet chemotherapy vs chemotherapy alone as neoadjuvant treatment for ...

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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

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Selected safety profile - Opdivo In Checkmate 816, serious adverse reactions occurred in 30% of patients (n=176) who were treated with OPDIVO in combination with platinum-doublet chemotherapy.

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a four arms phase Ib study This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with ...