Neoadjuvant Immunotherapy for Mesothelioma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of immune-boosting drugs, nivolumab and ipilimumab, to determine if they can safely help the body fight mesothelioma (a type of cancer affecting the lining of the lungs) before surgery. The research targets patients whose tumors can potentially be removed through surgery. Participants may receive either nivolumab alone or both drugs together before their surgery. This trial could suit individuals with specific types of mesothelioma who are eligible for surgery and can undergo a tumor biopsy. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that nivolumab, when used alone, has not raised new safety concerns for patients with malignant pleural mesothelioma. A study in Japan found no unexpected side effects, indicating it is generally well-tolerated. However, nivolumab can cause serious side effects in some cases, such as lung problems or pneumonia.

When combined with ipilimumab, this combination is already approved for treating newly diagnosed mesothelioma. A study with 135 patients showed the treatment is generally safe, though serious side effects can occur. These include immune-related reactions, with about 3.6% of patients experiencing life-threatening issues.

Both treatments, whether used alone or together, have been tested in multiple studies, showing they are generally safe but can have serious side effects for some people. It is important to discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they use immunotherapy to tackle mesothelioma, a cancer traditionally treated with surgery, chemotherapy, and radiation. Ipilimumab and Nivolumab are unique because they are immune checkpoint inhibitors that help the body's immune system recognize and attack cancer cells more effectively. Unlike standard treatments that often suppress the immune system, these drugs enhance immune activity, offering a new angle in cancer treatment. The combination of Nivolumab with Ipilimumab in one arm of the study is particularly promising, as it targets two different pathways to potentially boost effectiveness. This approach could lead to better outcomes and provide hope for patients with this challenging condition.

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

Research has shown that using nivolumab before surgery is safe and has enabled many mesothelioma patients to proceed to surgery. In this trial, participants in Arm A will receive nivolumab only. Past studies have shown that about 81% of individuals in similar groups underwent surgery after this treatment. Participants in Arm B will receive a combination of nivolumab and ipilimumab, which has also yielded encouraging results, with patients living longer compared to past data. Both treatments are associated with longer survival times, particularly when used together. Overall, these findings suggest that these treatments could be more effective in managing mesothelioma than traditional methods. ^{6 7 8 9 10}

Who Is on the Research Team?

Julie Brahmer, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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]

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 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 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 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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8003

Feasibility and safety of neoadjuvant nivolumab ... Neoadjuvant platinum, pemetrexed, and nivolumab was reliably able to be given to patients with DPM without impacting their ability to undergo P/D.

2. esmo.org esmo.org/oncology-news/feasibility-of-neoadjuvant-immune-checkpoint-blockade-for-resectable-diffuse-pleural-mesothelioma-along-potential-of-ctdna-analyses-to-detect-residual-disease

Feasibility of Neoadjuvant Immune Checkpoint Blockade ... The study met its primary endpoints, and, in arms A and B, 81.3% and 85.7% of patients proceeded to surgery. Treatment was safe, with a single ...

3. nature.com nature.com/articles/s41591-025-03958-3

a phase 2 trial and ctDNA analyses | Nature Medicine Treatment was safe, with a single dose-limiting toxicity in each arm. In Arm A, median PFS and OS were 9.6 months (95% confidence interval (CI): ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11853238/

Recent Advances in Mesothelioma Treatment: Immunotherapy ... The 3- and 4-year follow-up studies of CheckMate-743 showed the consistent superiority of the nivolumab/ipilimumab combination therapy compared to chemotherapy ...

5. opdivohcp.com opdivohcp.com/efficacy/nsclc/77t

See the impact of pCR* in your patients 2,3 - Opdivo View efficacy information for perioperative OPDIVO® (nivolumab) + chemotherapy in resectable non-small cell lung cancer (NSCLC). Please see Indications and ...

6. opdivohcp.com opdivohcp.com/safety

Safety Information | OPDIVO® (nivolumab) The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S016950022500594X

First-line nivolumab plus ipilimumab in pleural mesothelioma In this retrospective, multicenter study, the outcome and safety data for 135 consecutive patients with first-line nivolumab/ipilimumab were evaluated among ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631123/

Real-world safety of nivolumab in patients with malignant ... In this post-marketing surveillance study of nivolumab in patients with malignant pleural mesothelioma in Japan, no new safety signals were identified.

9. opdivo.com opdivo.com/malignant-pleural-mesothelioma/getting-treatment

Getting treatment for malignant pleural mesothelioma It is not known if OPDIVO is safe and effective in children younger than 12 years of age with melanoma or MSI-H or dMMR metastatic colorectal cancer. It is not ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7481613/

Nivolumab in pre-treated malignant pleural mesothelioma Randomized phase III trials are ongoing to investigate the efficacy of nivolumab in malignant pleural mesothelioma (MPM), but real-world data are still scarce.