MEDI5752 + Chemotherapy for Pleural Mesothelioma
(eVOLVE-Meso Trial)
Recruiting in Palo Alto (17 mi)
+144 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: Chemotherapy, Radiotherapy, Biologics, Hormonal
Disqualifiers: Autoimmune disorders, Other malignancy, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
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.
12345Is 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.
13678What 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.
134910Eligibility Criteria
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.
I am 18 years old or older.
My organs and bone marrow are working well.
+3 more
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.
+4 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Volrustomig + Carboplatin + pemetrexedExperimental Treatment3 Interventions
Volrustomig in combination with carboplatin plus pemetrexed
Group II: Investigator's choice of standard careActive Control5 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteBaltimore, MD
Research SiteIndependence, OH
Research SiteColumbus, OH
Research SiteValhalla, NY
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. [2015]Pemetrexed has established efficacy, and is the backbone for chemotherapy in patients with malignant pleural mesothelioma (MPM). An International Expanded Access Program provided >3000 mesothelioma patients with access to single-agent pemetrexed or pemetrexed plus platinum analogs (cisplatin or carboplatin) in 13 countries. In this article, we report the safety and efficacy data of MPM patients who were treated with single-agent pemetrexed (n = 812).
Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. [2022]This multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM).
Immunotherapy in Malignant Pleural Mesothelioma. [2020]The only registered systemic treatment for malignant pleural mesothelioma (MPM) is platinum based chemotherapy combined with pemetrexed, with or without bevacizumab. Immunotherapy did seem active in small phase II trials. In this review, we will highlight the most important immunotherapy-based research performed and put a focus on the future of MPM. PD-(L)1 inhibitors show response rates between 10 and 29% in phase II trials, with a wide range in progression free (PFS) and overall survival (OS). However, single agent pembrolizumab was not superior to chemotherapy (gemcitabine or vinorelbine) in the recent published PROMISE-Meso trial in pre-treated patients. In small studies with CTLA-4 inhibitors there is evidence for response in some patients, but it fails to show a better PFS and OS compared to best supportive care in a randomized study. A combination of PD-(L)1 inhibitor with CTLA-4 inhibitor seem to have a similar response as PD-(L)1 monotherapy. The first results of combining durvalumab (PD-L1 blocking) with cisplatin-pemetrexed in the first line are promising. Another immune treatment is Dendritic Cell (DC) immunotherapy, which is recently tested in mesothelioma, shows remarkable anti-tumor activity in three clinical studies. The value of single agent checkpoint inhibitors is limited in MPM. There is an urgent need for biomarkers to select the optimal candidates for immunotherapy among MPM patients in terms of efficacy and tolerance. Results of combination checkpoint inhibitors with chemotherapy are awaiting.
Overview on ongoing or planned clinical trials in Europe. [2015]Malignant pleural mesothelioma (MPM) is a locally invasive malignancy, but only a minority of patients can benefit by surgical resection. Among chemotherapeutic agents only vinorelbine, edatrexate, gemcitabine and raltitrexed have demonstrated response rates >20%. The largest randomised trial in MPM showed an improved median survival with cisplatin and pemetrexed versus cisplatin alone from 9.3 to 12.1 months. For the present overview about 70 requests of information were sent to the major European centres of thoracic oncology. The most widespread study treatment in Europe is an 'Extended Access Program (EAP)' evaluating pemetrexed alone or combined with cisplatin or carboplatin with about 1500 enrolled patients. Two other international randomized studies compare pemetrexed plus best supportive care (BSC) versus BSC alone, and the role of Ranpirnase (Onconase) in MPM. Important national trials are ongoing: in the UK the addressed questions were the role of radical surgery (MARS Trial), the role of chemotherapy (MS-01 trial) and the role of VATS on active treatment of pleural effusion. In Switzerland the SAKK group phase III study explores in a comparative way the value of hemithoracic radiotherapy after primary treatment with cisplatin/pemetrexed followed by surgery. In Italy, 2 phase II trials of neoadjuvant chemotherapy (pemetrexed plus cisplatin in Rome, pemetrexed plus carboplatin in Padua) followed by surgery and radiotherapy are active. With the important exception of UK, the most evident element is the overwhelming presence of pemetrexed in the ongoing and future clinical trials. Pemetrexed has influenced not only the clinical practice, but also the patient enrolment in clinical trials.
Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. [2020]Single-drug checkpoint inhibition has shown efficacy in patients with recurrent malignant pleural mesothelioma. Here, we assessed the safety and efficacy of the combination of nivolumab, an anti-programmed cell death 1 antibody, plus ipilimumab, an anti-cytotoxic T-lymphocyte protein 4 antibody, in patients with previously treated and relapsed malignant pleural mesothelioma.
FDA drug approval summaries: pemetrexed (Alimta). [2022]The purpose of this report is to summarize information on pemetrexed (LY231514; MTA; Alimta; Eli Lilly and Company; Indianapolis, IN), a drug recently approved by the U.S. Food and Drug Administration (FDA). The review of the efficacy and safety of pemetrexed is summarized below. Pemetrexed is a pyrrolopyrimidine antifolate. It inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and dihydrofolate reductase. In a single, randomized, single-blind, multicenter phase III trial, the efficacy and safety of pemetrexed combined with cisplatin (Platinol; Bristol-Myers Squibb; Princeton, NJ) were compared with those of single-agent cisplatin in 448 patients with malignant pleural mesothelioma. Two hundred twenty-six patients were randomized to receive pemetrexed and cisplatin, while 222 patients were randomized to receive cisplatin alone. The primary study end point was survival. Median survival times were 12.1 months for the pemetrexed plus cisplatin treated arm and 9.3 months for the cisplatin alone arm. Pemetrexed causes myelosuppression. The most common adverse events were neutropenia, fatigue, leukopenia, nausea, dyspnea, and vomiting. On February 4, 2004, pemetrexed was approved by the FDA in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) administered as an i.v. infusion over 10 minutes on day 1 of each 21-day cycle together with cisplatin at a dose of 75 mg/m(2) infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B(12) injections prior to the start of therapy and continue these during therapy to reduce severe toxicities. Patients should also receive corticosteroids with chemotherapy to reduce the risk of skin rashes. Approval was based on superior survival as a clinical benefit.
The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma. [2022]We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma.
Brief Report: Canadian Cancer Trials Group IND.227: A Phase 2 Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT02784171). [2023]Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase 2 trial (120 patients planned) comparing progression-free survival of standard platinum and pemetrexed (CP) versus CP + pembrolizumab (pembro) versus pembro. Accrual to the pembro arm was discontinued on the basis of interim analysis (IA-16 wk disease control rate). CP + pembro was tolerable, with progression-free survival similar between arms and median survival and overall response rate higher than those of CP alone (19.8 mo [95% confidence interval or CI: 8.4-41.36] versus 8.9 mo [95% CI: 5.3-12.8] and 47% [95% CI: 24%-71%] versus 19% [95% CI: 5%-42%], respectively). The subsequent phase 3 trial has completed accrual; results are expected in 2023.
Pemetrexed in the treatment of malignant mesothelioma: results from an expanded access program in Germany. [2015]An international expanded access program was initiated to provide access to treatment with pemetrexed prior registration and reimbursement for malignant mesothelioma (MM). Chemonaïve and pretreated patients with inoperable MM of the pleura or peritoneum were eligible. This report describes the results obtained in German centers. Investigators could choose between three treatments: Pemetrexed 500 mg/m(2) alone (P) or in combination with cisplatin 75 mg/m(2) (PC) or carboplatin AUC 5 (PCb). From November 2002 to June 2004, a total of 567 patients (554 with pleural MM; 41% pretreated) were included. Of 548 evaluable patients with pleural MM, 191 received P, 137 PC and 220 PCb. Patients in the P group were more often pretreated (70%) and had worse performance status compared with the other groups. In the P, PC, and PCb groups overall response rate (ORR) was 16%, 24% and 18%, median time to progression (TTP) was 5.5, 8.2, and 6.9 months, and median overall survival (OS) was 8.7, 11.3 and 9.7 months respectively. Efficacy outcomes were better for chemonaïve than for pretreated patients, and P was less hematotoxic than PC or PCb. Treatment of pleural MM with pemetrexed alone or in combination with platinum was safe and active as first and second-line therapy.
Pemetrexed in malignant pleural mesothelioma. [2015]This report describes the data and analysis leading to the approval of pemetrexed (LY 231514, MTA, Alimta, Eli Lilly and Co., Indianapolis, IN) by the U.S. Food and Drug Administration (FDA) of a New Drug Application for the treatment of malignant pleural mesothelioma (MPM).