Pre-Surgery Immunotherapy for Mesothelioma

Recruiting at 121 trial locations

Overseen By Aaron Mansfield, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Immunosuppressants

Disqualifiers: Unresectable, Chest wall invasion, 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: 1

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether using immunotherapy drugs, nivolumab and ipilimumab, before surgery can better control sarcomatoid mesothelioma, a type of lung cancer. These drugs boost the immune system to attack cancer cells and may help stop the cancer from growing and spreading. The trial targets individuals with stage I-IIIa sarcomatoid mesothelioma who haven't received prior treatments for their cancer. Participants will receive the drugs through an IV and may undergo surgery, with several scans (such as CT or MRI) to monitor progress.

As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you cannot have treatment with hormones or other chemotherapeutic agents, except for hormones used for non-disease-related conditions like insulin for diabetes.

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

Research has shown that the combination of nivolumab and ipilimumab has been tested for safety in people with pleural mesothelioma. In one study, 135 patients received this treatment, and researchers monitored their safety. The results showed that most patients tolerated the treatment well. However, like any treatment, some side effects occurred, such as tiredness, skin rash, and diarrhea. Most patients found these side effects manageable. Another study found that the response to this treatment was similar to traditional chemotherapy but with different side effects. Overall, these studies suggest that the nivolumab and ipilimumab combination is safe, with side effects that are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ipilimumab and Nivolumab for mesothelioma because it represents a shift from traditional chemotherapy-based treatments to immunotherapy. Unlike standard treatments that typically attack cancer cells directly, these drugs work by boosting the body's immune system to recognize and destroy cancer cells more effectively. Ipilimumab and Nivolumab are both checkpoint inhibitors, which help to unleash the immune system by blocking proteins that prevent immune cells from attacking cancer. This innovative approach has the potential to improve outcomes for patients by enhancing the body's natural defenses against cancer, possibly leading to better survival rates and quality of life.

What evidence suggests that this treatment might be an effective treatment for mesothelioma?

Research has shown that using the drugs nivolumab and ipilimumab together can help treat mesothelioma, a type of cancer. In a study with patients who had malignant pleural mesothelioma, those who received these two drugs had a 26% lower chance of dying compared to those who received standard chemotherapy. This suggests the drug combination may help the immune system fight cancer cells more effectively. In this trial, participants will receive nivolumab and ipilimumab before surgery. The results indicate that using these drugs before surgery might better control a specific type of mesothelioma called sarcomatoid mesothelioma. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with stage I-IIIa sarcomatoid mesothelioma who haven't had prior treatments affecting the primary tumor. Candidates must have a stable HIV, no active infections or autoimmune diseases (with some exceptions), and an ECOG performance status of <=2 or Karnofsky >=60%. Pregnant or nursing women are excluded, as well as those with certain heart conditions or other health issues that could interfere with surgery.

Inclusion Criteria

I haven't received treatments that would affect the main goal of this study.

Your predicted lung function is expected to be more than 35% of normal after surgery.

You have a disease that can be measured or a disease that cannot be measured according to specific guidelines.

Exclusion Criteria

My cancer has not spread to my chest wall, abdomen, opposite lung side, mid-chest organs, spine, or above my collarbone.

I am considered a good candidate for surgery.

I have never had symptomatic interstitial lung disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Immunotherapy

Participants receive nivolumab and ipilimumab intravenously before surgery

12 weeks

Regular visits for IV administration and monitoring

Surgery

Participants may undergo surgery after neoadjuvant immunotherapy

Immediate post-immunotherapy

1 visit (in-person for surgery)

Follow-up

Participants are monitored for safety, effectiveness, and time to recurrence after surgery

Up to 5 years

Regular follow-up visits including CT, MRI, and PET scans

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Surgical Procedure

Trial Overview

The trial tests if giving immunotherapy drugs nivolumab and ipilimumab before surgery can better control sarcomatoid mesothelioma compared to immunotherapy alone. These drugs may boost the immune system's ability to fight cancer by targeting specific proteins on tumor cells.

How Is the Trial Designed?

Group I: Treatment (nivolumab, ipilimumab, surgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV, ipilimumab IV, and may undergo surgery on study. Patients also undergo CT or MRI and PET throughout the trial.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nivolumab combined with ipilimumab has been approved by the FDA as the first-line treatment for unresectable malignant pleural mesothelioma (MPM), showing improved overall survival (OS) of 18.1 months compared to 14.1 months for chemotherapy, based on a study of 605 patients.

The treatment was particularly more beneficial for patients with non-epithelioid histology, and the approval process involved collaboration with multiple international health agencies, marking the first new drug regimen for MPM since 2004.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma. Nakajima, EC., Vellanki, PJ., Larkins, E., et al.[2022]

The combination therapy of nivolumab and ipilimumab has been FDA approved for treating malignant pleural mesothelioma, showing improvements in overall survival, marking a significant advancement in treatment options since 2004.

A case study of a 35-year-old male revealed that this therapy can lead to serious side effects, such as digital ischaemia due to small vessel vasculitis, emphasizing the need for early detection and a multidisciplinary approach to manage complications effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma. Kefas, J., Harwood, C., Lewis, MJ., et al.[2022]

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.

The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Wright, K.[2021]

In the CheckMate 743 trial involving 605 patients with unresectable malignant pleural mesothelioma, the combination of nivolumab and ipilimumab significantly improved overall survival compared to chemotherapy.

Patient-reported outcomes indicated that nivolumab and ipilimumab not only delayed deterioration in health-related quality of life and disease-related symptoms but also maintained quality of life over time, with improvements noted in various symptom scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743. Scherpereel, A., Antonia, S., Bautista, Y., et al.[2022]

In a case study of 2 patients with metastatic peritoneal mesothelioma, the addition of the immune checkpoint inhibitor pembrolizumab to standard chemotherapy resulted in significant disease responses, including a substantial partial response and a near complete response.

Both patients had tumors lacking typical biomarkers for ICI response, suggesting that their unique tumor characteristics and the chemotherapy may have enhanced the effectiveness of the immune therapy, indicating a potential new treatment strategy for this rare cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Platinum Nonresponsive Metastatic Malignant Peritoneal Mesothelioma With Combination Chemoimmunotherapy. Foote, MB., Shia, J., Zauderer, MG., et al.[2023]

In a phase 2 trial involving 36 patients with recurrent malignant pleural mesothelioma, the combination of nivolumab and ipilimumab achieved disease control in 68% of patients at 12 weeks, indicating significant efficacy for this treatment approach.

The safety profile was consistent with previous studies, with 94% of patients experiencing treatment-related adverse events, primarily infusion reactions, skin disorders, and fatigue, suggesting that while effective, the combination therapy does have notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Disselhorst, MJ., Quispel-Janssen, J., Lalezari, F., et al.[2020]

In the phase III CheckMate 743 study, nivolumab plus ipilimumab significantly improved overall survival in patients with unresectable malignant pleural mesothelioma, with a median overall survival of 18.1 months compared to 14.1 months for chemotherapy, and 3-year overall survival rates of 23% versus 15%.

The combination treatment also showed a manageable safety profile, with no new safety signals reported, and even patients who discontinued due to treatment-related adverse events had a median overall survival of 25.4 months, indicating sustained benefits from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Peters, S., Scherpereel, A., Cornelissen, R., et al.[2022]

Immune checkpoint inhibitors (ICI) have shown variable efficacy in mesothelioma, with initial trials reporting objective response rates between 4.5% and 29%, and median overall survival ranging from 7.7 to 18.0 months, indicating a need for better treatment strategies.

A Phase 3 trial demonstrated that the combination of ipilimumab and nivolumab significantly improved overall survival compared to standard chemotherapy, establishing it as a new standard of care, particularly for non-epithelioid mesothelioma, although initial progression-free survival was lower in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma. Cui, W., Popat, S.[2021]

In a retrospective study of 11 patients with malignant pleural mesothelioma treated with nivolumab, 72.7% experienced immune-related adverse events (irAEs), which were linked to better treatment outcomes.

Patients with grade ≥2 irAEs had significantly longer progression-free survival (13.6 months) and overall survival (not reached) compared to those with milder irAEs, suggesting that monitoring and managing irAEs could enhance the effectiveness of nivolumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma. Yoneda, H., Nokihara, H., Mitsuhashi, A., et al.[2022]

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In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials.

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Opdivo (nivolumab) Plus Yervoy (ipilimumab) ...

Objective response rate (ORR) in patients treated with the combination was comparable to chemotherapy (39.6% vs. 44.0%, respectively). “The ...