Nivolumab + Temozolomide for Lung & Neuroendocrine Cancers

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dwight Owen

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, HIV, 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

Compensation: Varies

Number of Visits: 8

Duration: Up to 3 years

55 Participants Needed

Trial Summary

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 steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment. Also, if you are on a somatostatin analogue, you can continue as long as the dose is stable for at least 2 months.

What data supports the effectiveness of the drug Nivolumab for lung cancer?

Nivolumab has been shown to improve survival and response rates in patients with advanced non-small cell lung cancer (NSCLC) who have already received chemotherapy, as seen in studies like CheckMate 017 and CheckMate 057. It is better tolerated than the chemotherapy drug docetaxel, making it an important option for these patients. ^{1 2 3 4 5}

Is the combination of Nivolumab and Temozolomide safe for humans?

Nivolumab (also known as Opdivo) has been shown to have a manageable safety profile in patients with advanced non-small cell lung cancer, with side effects that are generally tolerable compared to other treatments like docetaxel. However, specific safety data for the combination of Nivolumab and Temozolomide is not provided in the available research. ^{1 2 3 6 7}

What makes the drug combination of Nivolumab and Temozolomide unique for treating lung and neuroendocrine cancers?

This drug combination is unique because it combines Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Temozolomide, a chemotherapy drug that damages the DNA of cancer cells, potentially offering a new treatment option for patients with limited choices, especially in advanced neuroendocrine neoplasms. ^{1 2 3 8 9}

What is the purpose of this trial?

This phase II trial studies how well nivolumab and temozolomide work in treating patients with small-cell lung cancer that has come back or does not respond to treatment, or neuroendocrine cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and temozolomide may work better in treating patients with small-cell lung cancer and neuroendocrine cancer.

Research Team

Dwight Owen, MD, MS

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with recurrent or unresponsive small-cell lung cancer, or advanced neuroendocrine tumors. Participants must have measurable disease progression and be able to take oral medication. They should not have had certain treatments like temozolomide before, and those with serious health conditions such as active hepatitis, CNS metastases, or autoimmune diseases are excluded.

Inclusion Criteria

You have advanced neuroendocrine tumor or carcinoma, and have shown signs of disease progression in the past year.

You are able to perform daily activities without any major issues.

For Cohort 2: Archival tissue as above is preferred, but not required for trial entry

Exclusion Criteria

You have active hepatitis B or hepatitis C.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 5 months (for females) or 7 months (for males) after the last dose of trial treatment

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab intravenously on day 1 and temozolomide orally on days 1-5 of a 28-day cycle. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Monthly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days post-treatment, then every 8 weeks for 12 months, and every 12 weeks thereafter.

Up to 3 years

Regular follow-up visits every 8-12 weeks

Treatment Details

Interventions

• Nivolumab
• Temozolomide

Trial Overview The trial tests the combination of nivolumab (an immunotherapy drug) and temozolomide (a chemotherapy drug) on patients. Nivolumab may boost the immune system's response against cancer cells while temozolomide aims to stop tumor growth by killing cells or preventing their division.

Participant Groups

Group I: Treatment (nivolumab, temozolomide) Experimental Treatment 2 Interventions

Patients receive nivolumab IV on day 1 of a 28 day cycle. Patients also receive temozolomide PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Dwight Owen

Lead Sponsor

Trials

6

Recruited

210+

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

A network meta-analysis of five trials showed that PD-1 inhibitors (pembrolizumab and nivolumab) had higher overall response rates (ORR) compared to the PD-L1 inhibitor (atezolizumab), particularly in patients with high PD-L1 expression.

Both pembrolizumab and nivolumab demonstrated superior overall survival (OS) benefits in various patient subgroups, but treatment decisions should also consider individual patient characteristics and safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. Almutairi, AR., Alkhatib, N., Martin, J., et al.[2019]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of immunotherapies targeting the PD-1/PD-L1 pathway for previously treated advanced non-small cell lung cancer: A Bayesian network meta-analysis. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

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

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

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

A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. [2019]