Neoadjuvant Immunotherapy for Mesothelioma

Recruiting at 2 trial locations

Overseen By Jasmine Brooks, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Unresectable disease, Autoimmune disease, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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: 4

30 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 corticosteroids or other immunosuppressive medications, you may need to stop them at least 14 days before starting the study drugs. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination of nivolumab and ipilimumab for treating mesothelioma?

The combination of nivolumab and ipilimumab was shown to improve overall survival in patients with unresectable malignant pleural mesothelioma, with patients living a median of 18.1 months compared to 14.1 months for those receiving standard chemotherapy, according to the CheckMate 743 study. ^{1 2 3 4 5}

What safety data exists for neoadjuvant immunotherapy using nivolumab and ipilimumab in humans?

Nivolumab and ipilimumab, used together, have been approved for treating malignant pleural mesothelioma, and studies show they can cause immune-related side effects, including skin issues. These treatments have been evaluated in various conditions, and while they can improve survival, they may also lead to adverse events like small vessel vasculitis (inflammation of blood vessels) and dry gangrene (tissue death due to lack of blood flow). ^{1 3 6 7 8}

How does neoadjuvant immunotherapy for mesothelioma differ from other treatments?

Neoadjuvant immunotherapy for mesothelioma, using nivolumab and ipilimumab, is unique because it leverages the body's immune system to fight cancer, unlike traditional chemotherapy. This combination has shown improved survival rates compared to standard chemotherapy and represents a new approach for treating this aggressive cancer. ^{1 3 5 8 9}

What is the purpose of this trial?

The proposed study will evaluate the safety and feasibility of neoadjuvant nivolumab +/- ipilimumab in resectable MPM. In addition, maintenance nivolumab will be administered for 1 year following completion of standard bi-/tri-modality therapy.

Research Team

Julie Brahmer, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

This trial is for adults with resectable malignant pleural mesothelioma (MPM), specifically epithelial or biphasic types, who are in good physical condition and have not received prior cancer therapy. They must be able to undergo a biopsy, have adequate organ function, and agree to use contraception. People with unresectable disease, sarcomatoid histology, interstitial lung disease, autoimmune diseases, infections like HIV/AIDS or hepatitis B/C, recent immunosuppressant use or allergies to study drugs cannot join.

Inclusion Criteria

My organs are functioning well.

Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception

I am fully active or can carry out light work.

Exclusion Criteria

I may need to start medications that affect my immune system during the study.

You have an ongoing autoimmune disease, except for certain specific conditions.

Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive preoperative nivolumab +/- ipilimumab prior to planned surgery

6 weeks

3 visits (in-person)

Surgery

Participants undergo planned surgery for resectable MPM

1 week

1 visit (in-person)

Maintenance Therapy

Participants receive maintenance nivolumab for 1 year following standard therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Treatment Details

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The trial tests the safety of using Nivolumab alone or combined with Ipilimumab before surgery in MPM patients. After standard treatments post-surgery, maintenance doses of Nivolumab will continue for one year to see if it helps keep the cancer from coming back.

Participant Groups

Group I: Arm B Nivolumab + Ipilimumab Experimental Treatment 2 Interventions

Receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Group II: Arm A Nivolumab Only Experimental Treatment 1 Intervention

Receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

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]

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 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]

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]

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 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]

References

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

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

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

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

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

The Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma. [2018]

5. 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]

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

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

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

Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. [2020]

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

Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes. [2019]