Nivolumab + Chemotherapy for Mesothelioma

Not currently recruiting at 8 trial locations

Overseen By Michael Offin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Systemic corticosteroids

Disqualifiers: Autoimmune disease, Active hepatitis, Active cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment plan for individuals with mesothelioma, a cancer affecting the lung lining. Researchers aim to determine if combining the immunotherapy drug nivolumab with chemotherapy drugs pemetrexed and either cisplatin or carboplatin before surgery is safe and effective. This trial targets those whose mesothelioma can potentially be removed by surgery. Individuals diagnosed with this type of cancer who have not previously received chemotherapy or immunotherapy may find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using prednisone at a dose of 10 mg or more daily, or if you have an autoimmune disease requiring treatment in the past two years.

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

Research has shown that the combination of nivolumab, pemetrexed, and cisplatin or carboplatin has been tested for safety. In studies with these drugs, most patients tolerated the treatment well. Some experienced side effects like tiredness, nausea, or changes in blood cell counts, but these were generally manageable.

As a Phase 1 trial, this stage is early in the testing process. The main goal is to assess the treatment's safety for people. These drugs have been used in other contexts, providing some confidence in their safety. However, because this specific combination is new, the trial will closely monitor for any unexpected effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining Nivolumab with chemotherapy for mesothelioma because it introduces a new mechanism of action. Unlike traditional treatments that primarily rely on chemotherapy alone, Nivolumab is an immunotherapy drug that helps the body's immune system recognize and attack cancer cells more effectively. This combination could potentially enhance the effectiveness of chemotherapy agents like Cisplatin or Carboplatin and Pemetrexed, offering a more powerful approach to tackling mesothelioma. This novel strategy might improve outcomes for patients by possibly shrinking tumors more effectively or slowing their growth compared to existing treatments.

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

In this trial, participants will receive a combination of the drug nivolumab with chemotherapy drugs pemetrexed and either cisplatin or carboplatin to treat mesothelioma. Research has shown that combining nivolumab with these chemotherapy drugs may help treat mesothelioma. One study found that using these drugs together produced promising results for patients with advanced mesothelioma, suggesting this combination could be effective. In Japan, nivolumab demonstrated positive effects when used after other treatments, highlighting its role in fighting mesothelioma. While more detailed information on survival rates is still needed, early evidence suggests this treatment approach might improve outcomes for patients with this challenging cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Offin

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with resectable malignant pleural mesothelioma. Participants must have a performance status indicating they are relatively active, agree to contraception if of childbearing potential, and not be pregnant or breastfeeding. They should not have had prior chemo or immunotherapy for mesothelioma, no serious illnesses or other cancers requiring treatment, and no active hepatitis B/C or HIV.

Inclusion Criteria

My surgeon believes my condition can be treated with surgery.

I can provide tissue samples for the study, either from previous procedures or by undergoing a new biopsy if safe.

You have a negative HIV blood test.

Exclusion Criteria

Pregnant or lactating women

I have received chemotherapy or immunotherapy for mesothelioma.

I currently have lung inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Participants receive two cycles of neoadjuvant therapy with nivolumab, pemetrexed, and either cisplatin or carboplatin

6 weeks

Surgery

Participants undergo pleurectomy/decortication

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin or Carboplatin
• Nivolumab
• Pemetrexed
• Surgery

Trial Overview The study tests the combination of Nivolumab (an immunotherapy drug) with chemotherapy drugs Pemetrexed and either Cisplatin or Carboplatin before surgery in patients with mesothelioma. It aims to determine if this approach is safe and effective without delaying surgical intervention.

How Is the Trial Designed?

Group I: nivolumab with pemetrexed and cisplatin or carboplatin Experimental Treatment 3 Interventions

Eligible patients will receive two cycles of neoadjuvant therapy with nivolumab 360 mg, pemetrexed 500 mg/m2, and cisplatin 75 mg/m2 or carboplatin AUC=5. Subsequently, they will undergo pleurectomy/decortication.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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 903 patients with malignant pleural mesothelioma (MPM), pemetrexed combined with cisplatin was found to be generally well tolerated, with a low treatment-associated death rate of 0.8% and an interstitial lung disease (ILD) incidence of 0.9%.

The overall response rate to treatment was 25%, and the six-month survival rate was estimated at 75.9%, indicating that pemetrexed is effective in managing MPM, consistent with previous clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of pemetrexed in patients with malignant pleural mesothelioma based on all-case drug-registry study. Kuribayashi, K., Voss, S., Nishiuma, S., et al.[2015]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

In a study of 51 patients with malignant pleural mesothelioma, both pemetrexed with carboplatin (AC) and pemetrexed with cisplatin (AP) were found to be effective neoadjuvant chemotherapy regimens, with similar rates of disease control and surgical resection (81% for AC and 79% for AP).

However, the AP regimen was associated with a higher incidence of severe side effects, such as grade 3 anemia and increased fatigue, which could negatively affect patients' overall health and their ability to undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). Pasello, G., Marulli, G., Polo, V., et al.[2015]

Pemetrexed, often combined with cisplatin or carboplatin, is the most widely studied treatment for malignant pleural mesothelioma (MPM) in Europe, with around 1500 patients enrolled in an Extended Access Program, showing improved survival rates compared to other treatments.

The largest randomized trial indicated that combining pemetrexed with cisplatin improved median survival from 9.3 to 12.1 months, highlighting its efficacy in treating MPM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview on ongoing or planned clinical trials in Europe. Favaretto, A.[2015]

In a study involving 812 patients with malignant pleural mesothelioma (MPM), single-agent pemetrexed showed promising efficacy, with a median time to progressive disease of 6.0 months for chemonaïve patients and an overall response rate of 10.5%.

The treatment was well-tolerated, exhibiting mild hematologic toxicity, primarily neutropenia, in less than 18% of patients, indicating a favorable safety profile for pemetrexed in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. Taylor, P., Castagneto, B., Dark, G., et al.[2015]

In a study of 49 patients with malignant pleural mesothelioma, the combination of carboplatin and pemetrexed achieved a disease control rate of 69% and a median overall survival of 14 months, indicating its effectiveness as a treatment option.

The treatment was generally well-tolerated, with only 14.3% of patients experiencing severe haematological toxicities and 24.5% experiencing severe non-haematological toxicities, and no toxic deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option? Li, L., Razak, AR., Hughes, A.[2015]

In a study of 146 patients with malignant pleural mesothelioma, the combination of cis/carboplatin plus gemcitabine showed similar median survival rates (11.0 months) compared to cis/carboplatin plus pemetrexed (12.0 months), indicating that both treatment regimens are comparably effective.

Both treatment combinations were well tolerated with similar side effects, suggesting that cis/carboplatin plus gemcitabine is a safe alternative for patients, warranting further investigation in larger randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. Ak, G., Metintas, S., Akarsu, M., et al.[2022]

The first-line chemotherapy for locally advanced or metastatic mesothelioma is a combination of cisplatin and pemetrexed, which has been shown to be effective since its approval in 2004.

Recent studies involving nearly 200 patients indicate that combinations of anti-metabolites like gemcitabine with platinum salts can lead to a one-year survival rate of about 50%, highlighting their potential as promising treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mesothelioma: advances in chemotherapy]. Jacoulet, P.[2007]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8557301/

JME-001 phase II trial of first-line combination chemotherapy ... Outcomes. This study assessed the efficacy and safety of first-line combination therapy with cisplatin, pemetrexed, and nivolumab for advanced or metastatic MPM ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8560642/

Nivolumab versus placebo in patients with relapsed malignant ... No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0169500225006014

Pemetrexed plus platinum as second-line treatment for ... This retrospective observational study aimed to elucidate the efficacy of pemetrexed-platinum therapy as a second-line treatment for pleural ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02899299

NCT02899299 | Study of Nivolumab Combined With ... The purpose of this study is to test the effectiveness and tolerability of the combination of Nivolumab and Ipilimumab compared to Pemetrexed and Cisplatin ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9052

Efficacy and safety of nivolumab for malignant ... Nivolumab, an anti-programmed death-1 monoclonal antibody, shows efficacy against pretreated MPM and has been approved in Japan, but the data ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1525730418301062

A Phase II Trial of First-Line Combination Chemotherapy ... This study will assess the efficacy and safety of the first-line combination therapy of cisplatin, pemetrexed, and nivolumab for advanced or metastatic MPM.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05136677

NCT05136677 | A Study to Evaluate Nivolumab in ... The purpose of this study is to assess the efficacy and safety of the combination of nivolumab and ipilimumab in Chinese participants with malignant pleural ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.TPS8581

Checkmate 743: A phase 3, randomized, open-label trial ... Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment ...