MEDI5752 + Chemotherapy for Pleural Mesothelioma

(eVOLVE-Meso Trial)

Recruiting at 181 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Chemotherapy, Radiotherapy, Biologics, Hormonal

Disqualifiers: Autoimmune disorders, Other malignancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 months

825 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with pleural mesothelioma, a type of cancer affecting the lung lining. Researchers aim to determine if combining the experimental drug Volrustomig with chemotherapy drugs Carboplatin and Pemetrexed is more effective than current standard treatments. The trial includes two groups: one receiving the new treatment and the other receiving standard care options, such as other drug combinations. Ideal candidates for this trial are those diagnosed with advanced pleural mesothelioma that cannot be surgically removed. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving any chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.

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

Research shows that the treatments in this trial have varying safety levels. Here's a simple breakdown:

1. **Volrustomig (MEDI5752)**: This drug is a new cancer treatment that aids the immune system in fighting cancer. Its safety is still under study, and while it may have side effects common to similar treatments, further research is needed to fully understand its safety.

2. **Carboplatin**: This drug is generally safe for patients with pleural mesothelioma, a type of cancer. It works as effectively as other chemotherapy drugs, and its side effects can usually be managed.

3. **Pemetrexed**: This drug effectively treats mesothelioma and has a well-established safety record. It helps improve survival rates and is usually well tolerated by patients.

In summary, carboplatin and pemetrexed are known to be safe for treating mesothelioma. Volrustomig is still under study but represents a new approach in cancer treatment. Participants should consider these factors and consult their healthcare providers when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Volrustomig for pleural mesothelioma because it offers a novel approach compared to standard treatments like nivolumab plus ipilimumab or platinum-based chemotherapy. Volrustomig is unique because it combines with carboplatin and pemetrexed, potentially enhancing the immune response against cancer cells by targeting specific pathways that aren't addressed by current therapies. This innovative combination aims to improve efficacy and provide better outcomes for patients with pleural mesothelioma, particularly by leveraging the immune system in a new and potentially more effective way.

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

Research suggests that Volrustomig, a new treatment, could help treat pleural mesothelioma. This special type of antibody targets two proteins, PD-1 and CTLA-4, which cancer cells use to evade the immune system. By targeting these proteins, Volrustomig may enable the immune system to attack cancer cells more effectively. Early studies have shown promise in treating other cancers, such as advanced kidney cancer. In this trial, one group of participants will receive Volrustomig combined with two other drugs, carboplatin and pemetrexed, to determine if this combination can better halt cancer growth and support the immune system in fighting mesothelioma. Another group will receive the investigator's choice of standard care, which may include nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy, depending on the mesothelioma's histology. ^{6 7 8 9 10}

Who Is on the Research Team?

Marjorie Zauderer, MD

Principal Investigator

Memorial Slone Kettering (MSK) Cancer Centre

Arnaud Scherpereel, MD

Principal Investigator

Lille University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced, inoperable pleural mesothelioma. They must have stable health without significant deterioration in the past two weeks and measurable disease per specific criteria. Excluded are those with certain infections (TB, HBV, HCV, HIV), autoimmune or inflammatory disorders, another primary cancer (with exceptions), uncontrolled illnesses, or untreated brain metastases.

Inclusion Criteria

My cancer is confirmed as pleural mesothelioma and its type is known.

My organs and bone marrow are working well.

My condition cannot be cured with surgery.

Exclusion Criteria

I have or had an autoimmune or inflammatory disorder.

I do not have uncontrolled TB, HBV, HCV, or HIV.

I have had another type of cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Volrustomig (MEDI5752) in combination with Carboplatin and Pemetrexed or the investigator's choice of standard care

Up to 52 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Pemetrexed
• Volrustomig

Trial Overview The study compares the effectiveness of Volrustomig combined with Carboplatin and Pemetrexed against either platinum plus Pemetrexed or Nivolumab plus Ipilimumab. It's a phase III trial where participants are randomly assigned to receive one of these treatments to see which works best for unresectable pleural mesothelioma.

How Is the Trial Designed?

Group I: Volrustomig + Carboplatin + pemetrexed Experimental Treatment 3 Interventions

Volrustomig in combination with carboplatin plus pemetrexed

Group II: Investigator's choice of standard care Active Control 5 Interventions

The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a study involving 567 patients with malignant mesothelioma, pemetrexed alone or in combination with cisplatin or carboplatin showed overall response rates of 16%, 24%, and 18%, respectively, indicating that these treatments are effective options for managing this condition.

Pemetrexed alone was found to be less toxic to the blood compared to the combination therapies, suggesting it may be a safer option for patients, especially those who have already undergone treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. Reck, M., Stahel, RA., von Pawel, J., 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 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]

Current standard treatment for malignant pleural mesothelioma (MPM) involves platinum-based chemotherapy with pemetrexed, but immunotherapy has shown limited efficacy, with PD-(L)1 inhibitors yielding response rates of only 10-29% in phase II trials.

Recent studies indicate that single-agent immunotherapies like pembrolizumab do not outperform traditional chemotherapy, highlighting the need for better biomarkers to identify which patients might benefit from immunotherapy and the potential of combining immunotherapy with chemotherapy for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Malignant Pleural Mesothelioma. de Gooijer, CJ., Borm, FJ., Scherpereel, A., et al.[2020]

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 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]

In a phase II clinical study involving 102 patients with malignant pleural mesothelioma, the combination of pemetrexed and carboplatin resulted in an objective response rate of 18.6%, with 65.7% of patients achieving disease control.

The treatment was well tolerated, with mild toxicity reported; grade 3 or 4 neutropenia occurred in 9.7% of cycles, and the median overall survival was 12.7 months, suggesting that this combination could be a viable alternative to the standard treatment with pemetrexed and cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. Ceresoli, GL., Zucali, PA., Favaretto, AG., et al.[2022]

In a phase 2 trial involving 120 patients, the combination of standard chemotherapy (platinum and pemetrexed) with pembrolizumab (CP + pembro) showed improved median survival (19.8 months) and overall response rate (47%) compared to chemotherapy alone (8.9 months and 19%, respectively).

The addition of pembrolizumab to chemotherapy was found to be tolerable, and although the progression-free survival was similar between the treatment arms, the combination therapy demonstrated better outcomes, leading to the continuation of research in a phase 3 trial with results expected in 2023.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171). Piccirillo, MC., Chu, Q., Bradbury, P., et al.[2023]

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]

Pemetrexed, in combination with cisplatin, significantly improved median survival for patients with unresectable malignant pleural mesothelioma (MPM), with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a randomized trial of 448 patients.

The treatment was associated with common side effects such as myelosuppression (especially neutropenia), fatigue, and nausea, but patients are advised to take folic acid and vitamin B12 to help reduce severe toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in malignant pleural mesothelioma. Hazarika, M., White, RM., Booth, BP., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06097728

Study Details | NCT06097728 | MEDI5752 in Combination ... This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed

2. withpower.com withpower.com/trial/phase-3-mesothelioma-10-2023-49ddb

MEDI5752 + Chemotherapy for Pleural Mesothelioma Trial Overview The study compares the effectiveness of Volrustomig combined with Carboplatin and Pemetrexed against either platinum plus Pemetrexed or Nivolumab ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12320366/

Bispecific antibodies: unleashing a new era in oncology ... Advancements in diagnostic and therapeutic standards have substantially enhanced the survival of patients with malignant tumors.

4. mskcc.org mskcc.org/cancer-care/clinical-trials/24-236

A Phase 3 Study of Volrustomig (MEDI5752) in ... In this study, researchers are comparing a new combination drug treatment with other standard treatments for pleural mesothelioma.

5. urotoday.com urotoday.com/conference-highlights/esmo-2023/esmo-2023-kidney-cancer/147556-esmo-2023-medi5752-volrustomig-a-novel-pd-1-ctla-4-bispecific-antibody-in-the-first-line-1l-treatment-of-65-patients-pts-with-advanced-clear-cell-renal-cell-carcinoma-arcc.html

ESMO 2023: MEDI5752 (Volrustomig), a Novel PD-1/CTLA ... Volrustomig is a monovalent PD-1/CTLA-4 bispecific monoclonal antibody, which distinctly achieves full PD-1 blockade plus preferential CTLA-4 inhibition on ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18978569/

Treatment of malignant pleural mesothelioma with ... There were 56 responses (32.4%), of which 2 were complete; the median time to progression was 8.6 months, and the median overall survival was 13 months. Some ...

7. ilcn.org ilcn.org/real-world-data-show-that-survival-just-as-good-with-carboplatin-therapy-as-with-cisplatin-therapy-in-malignant-pleural-mesothelioma/

Real-World Data Show That Survival Just as Good With ... The largest real-world cohort study of individuals with malignant pleural mesothelioma (MPM) found a median survival duration of 8 months ...

8. asbestos.com asbestos.com/treatment/chemotherapy/carboplatin/

Carboplatin for Mesothelioma: Chemo Drug Overview & ... Carboplatin is safe, it's effective, it's tolerable, and it has a similar progression-free survival and overall survival [in pleural mesothelioma]. Thus, we ...

9. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2021-0047

Full article: Treatment Patterns and Outcomes of Patients ... Median overall survival for first-line SACT was 12.0 months (95% CI: 10.7–14.2). Results were similar with pemetrexed + cisplatin and pemetrexed + carboplatin.

10. nature.com nature.com/articles/s41598-021-00831-4

Efficacy of chemotherapy for malignant pleural ... The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was ...