Pre-Surgery Immunotherapy for Mesothelioma

Recruiting at115 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Immunosuppressants

Disqualifiers: Unresectable, Chest wall invasion, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests if giving immunotherapy drugs can better control disease in patients with a specific type of mesothelioma. The drugs help the immune system attack cancer cells, which may stop the cancer from growing and spreading.

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.

What data supports the effectiveness of the drugs Ipilimumab, Yervoy, Nivolumab, and Opdivo for treating mesothelioma?

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) has been shown to improve overall survival in patients with unresectable malignant pleural mesothelioma, as demonstrated in the CheckMate 743 trial. Patients receiving these drugs lived longer compared to those receiving standard chemotherapy. ^{1 2 3 4 5}

Is the combination of nivolumab and ipilimumab safe for humans?

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) has been approved by the FDA for treating malignant pleural mesothelioma, and skin-related side effects are the most common. While these drugs are generally considered safe, they can cause immune-related side effects, so it's important to discuss potential risks with your doctor. ^{1 5 6 7 8}

How is the drug combination of Ipilimumab and Nivolumab unique for treating mesothelioma?

The combination of Ipilimumab and Nivolumab is unique for treating mesothelioma because it is the first FDA-approved drug regimen for this condition since 2004, offering improved overall survival compared to traditional chemotherapy, especially in patients with non-epithelioid subtypes. ^{1 4 5 6 9}

Research Team

Eligibility Criteria

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 am 18 years old or older.

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.

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.

Trial Timeline

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

Treatment Details

Interventions

• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)
• Surgical Procedure (Surgery)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

Suzanne George

Alliance for Clinical Trials in Oncology

Chief Medical Officer since 2015

MD from Harvard Medical School

Evanthia Galanis

Alliance for Clinical Trials in Oncology

Chief Executive Officer since 2022

MD from Mayo Clinic

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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 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]

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]

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]

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]

References

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

FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma. [2022]

2. Ireland 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. [2022]

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

Treatment of Platinum Nonresponsive Metastatic Malignant Peritoneal Mesothelioma With Combination Chemoimmunotherapy. [2023]

4. England 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. [2022]

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

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

6. England 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Correlation between immune-related adverse events and therapeutic effects of nivolumab in patients with malignant pleural mesothelioma. [2022]

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

Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma. [2021]