Nivolumab + Temozolomide for Lung & Neuroendocrine Cancers

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, nivolumab and temozolomide, in treating certain types of cancer. Nivolumab, an immunotherapy drug, helps the immune system attack cancer cells, while temozolomide, a chemotherapy drug, stops cancer cells from growing and spreading. The trial targets patients with small-cell lung cancer that has returned or not responded to treatment and neuroendocrine cancer that has spread. Individuals whose small-cell lung cancer has returned after chemotherapy or whose neuroendocrine cancer has progressed in the past year might be suitable candidates. As a Phase 2 trial, the research measures 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, 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.

Is there any evidence suggesting that nivolumab and temozolomide are likely to be safe for humans?

A study of nivolumab and temozolomide in patients with small-cell lung cancer showed promising results. Patients generally tolerated the treatment well. Some experienced side effects, mostly mild to moderate, and no unexpected safety issues were reported.

Another study focused on patients with neuroendocrine tumors using the same treatment. It found that the combination was manageable for most patients. Again, side effects were mostly mild or moderate, with no new safety concerns.

These results suggest that nivolumab and temozolomide can be used safely in people with certain types of cancer. However, monitoring side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nivolumab and temozolomide because it offers a novel approach to treating lung and neuroendocrine cancers. Unlike standard treatments that primarily rely on chemotherapy or targeted therapies, nivolumab works by boosting the immune system to better recognize and attack cancer cells. This immune checkpoint inhibitor, when combined with temozolomide, which damages cancer cell DNA, has the potential to enhance the overall effectiveness of treatment. This combination could offer a powerful one-two punch that not only targets cancer cells directly but also empowers the body's own defenses to fight the disease more effectively.

What evidence suggests that nivolumab and temozolomide might be effective for lung and neuroendocrine cancers?

This trial examines the combination of nivolumab and temozolomide for treating certain cancers. Research has shown promising results when using these drugs together. Specifically, patients with advanced neuroendocrine tumors have experienced positive outcomes. Studies on small-cell lung cancer unresponsive to other treatments found this drug combination effective. Nivolumab aids the immune system in attacking cancer cells, while temozolomide inhibits their growth. This combination is under study for its potential effectiveness in treating difficult cancers. ^{1 4 6 7 8}

Who Is on the Research Team?

Dwight Owen, MD, MS

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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, 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]

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]

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]

Citations

1. jto.org jto.org/article/S1556-0864(22)00402-6/fulltext

OA12.04 Efficacy of Nivolumab and Temozolomide in ... Nivolumab and TEM showed promising efficacy after first-line CIT in patients with ES-SCLC as 2 nd and 3 rd line of therapy and in patients with brain ...

2. onclive.com onclive.com/view/temozolomide-plus-nivolumab-shows-efficacy-in-previously-treated-es-sclc

Temozolomide Plus Nivolumab Shows Efficacy in ... Temozolomide in combination with nivolumab induced a promising overall response rates in patients who previously received chemotherapy for extensive-stage ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9932582/

A Phase II Clinical Trial of Nivolumab and Temozolomide for ... In a phase II trial of combination nivolumab and temozolomide in patients with advanced neuroendocrine tumors (NET) and carcinomas (NEC), we observed a response ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4121

Efficacy of nivolumab and temozolomide in advanced ... Here we present the final results for the NEN cohort of a phase 2 trial of combination nivolumab and TEM in patients with advanced NEN along ...

5. jnccn.org jnccn.org/view/journals/jnccn/18/3.5/article-pCLO20-054.xml?rskey=dPPHXl&result=2&print

CLO20-054: A Phase 2 Trial of Nivolumab and ... Here we present the interim efficacy analysis of the NET cohort of our phase 2 trial of combination nivolumab and TEM in patients with advanced NET and small ...

6. clinicaltrial.be clinicaltrial.be/en/details/6377?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Nivolumab and Temozolomide in Treating Patients With ... To evaluate the central nervous system (CNS) PFS of patients with small cell lung cancer (SCLC) treated with nivolumab and temozolomide.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36255391/

A Phase II Clinical Trial of Nivolumab and Temozolomide for ... We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-02050

Nivolumab and Temozolomide in Treating Patients with ... 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 ...