MEDI5752 + Chemotherapy for Pleural Mesothelioma

(eVOLVE-Meso Trial)

Recruiting at 151 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 is testing a new drug called Volrustomig combined with two chemotherapy drugs, Carboplatin and Pemetrexed. It targets adult patients with advanced pleural mesothelioma that cannot be removed by surgery. The treatment aims to help the immune system fight the cancer while also killing cancer cells directly.

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 the combination of MEDI5752 and chemotherapy safe for treating pleural mesothelioma?

Pemetrexed, a drug used in combination with chemotherapy for pleural mesothelioma, has been shown to cause side effects like low blood cell counts, tiredness, and nausea. Combining it with other treatments like PD-1/CTLA-4 inhibitors (a type of immune therapy) has shown promise, but more research is needed to fully understand the safety of these combinations. ^{1 2 3 4 5}

What makes the drug MEDI5752 + Chemotherapy unique for treating pleural mesothelioma?

The drug combination of MEDI5752 with chemotherapy is unique because it includes a bispecific antibody targeting both PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system. This approach aims to enhance the immune response against cancer cells, potentially offering a novel mechanism compared to traditional chemotherapy alone. ^{3 4 6 7 8}

What data supports the effectiveness of the drug combination MEDI5752 and chemotherapy for pleural mesothelioma?

Pemetrexed, a key component of the chemotherapy, has shown effectiveness in treating malignant pleural mesothelioma, especially when combined with platinum-based drugs like carboplatin. Immunotherapy, which includes drugs targeting PD-1 and CTLA-4 like MEDI5752, has shown some promise in small trials, although results vary and more research is needed to confirm its effectiveness in combination with chemotherapy. ^{3 4 6 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 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]

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]

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]

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]

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]

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 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 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]

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

Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]

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

Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Immunotherapy in Malignant Pleural Mesothelioma. [2020]

4. Ireland pubmed.ncbi.nlm.nih.gov

Overview on ongoing or planned clinical trials in Europe. [2015]

5. 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]

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

FDA drug approval summaries: pemetrexed (Alimta). [2022]

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

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. [2022]

8. United States 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). [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. [2015]

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

Pemetrexed in malignant pleural mesothelioma. [2015]