Key Takeaways
- The PrE0505 study was a phase 2 clinical trial that tested the immunotherapy drug durvalumab combined with standard chemotherapy (pemetrexed and cisplatin) in patients with malignant pleural mesothelioma that could not be surgically removed.
- The results were significant: patients in the study had a median overall survival of 20.4 months — compared to just 12 months for patients receiving chemotherapy alone.
- At 12 months, 70.4% of patients were still alive. At 24 months, 44.2% were still alive. Patients with the epithelioid subtype survived longer than two years.
- The study enrolled 55 patients from 15 cancer centers across the U.S. between June 2017 and June 2018. The median age was 68, and 82% were male.
- The most common side effects were anemia, fatigue, and nausea. Grade 3 or higher adverse events occurred in 65.5% of patients.
- Based on these promising results, a larger follow-up trial — the phase 3 PrE0506/DREAM3R trial — was developed to further compare durvalumab plus chemotherapy against chemotherapy alone.
For many years, the only approved systemic therapy for treating malignant pleural mesothelioma was cisplatin and pemetrexed combination therapy. The phase 2 DREAM study which involves durvalumab with chemotherapy, ended up resulting in a progression-free survival at six months. Additionally, combining the anti-PD-1 antibody nivolumab with the anti-CTLA-4 antibody ipilimumab improved survival for patients who were not previously treated, compared to chemotherapy.
PrE0505 Study on Mesothelioma Patients
PrE0505 was a phase 2, single-arm study in which patients were administered durvalumab once every three weeks, combined with their regular dose of pemetrexed and cisplatin. The study took place from June of 2017 to June of 2018. 55 mesothelioma patients were enrolled in the study from 15 community and academic cancer centers across the United States. Everyone in the study was over 18 and all of them had unresectable malignant pleural mesothelioma. The median age of the patients was 68 years old and 82 percent of them were males. 75% of the tumors were of the epithelioid variety. The median overall survival for patients that participated in the study was 20.4 months, which was a lot longer than 12 months, which was the overall survival of the control group.
The symptoms most reported from the treatment were anemia, fatigue and nausea. Treatment-emergent adverse events of grade 3 or higher occurred in 65.5 percent of patients.
Based on results from the DREAM study and the PrE0505 study, a new study was developed called the phase 3PrE0506/DREAM3R trial. This trial compares the effects of durvalumab with chemotherapy compared to just chemotherapy. Those with epithelioid mesothelioma who were enrolled in the PrE0505 study survived longer than two years.
Inclusion Criteria
Other inclusion criteria for the PrE0505 trial included a variety of different elements. For instance, the patient had to have measurable disease, “defined as at least one lesion that can be accurately assessed at baseline by computed tomography or magnetic resonance imaging and is suitable for repeated assessment.” They also must have had a minimum of 15 unstained tumor samples available. They had to have had an ECOG performance status of 0 or 1, they had to sign an informed consent and they had to have adequate organ function. Additionally, the patient could not be pregnant, they must not have participated in another study of the last four weeks and they must not have received any systemic therapy to treat their mesothelioma in the past. These are just a sampling of the many criteria.
Patrick Forde, MBBCh, an Associate Professor of Oncology at the Johns Hopkins University School of Medicine reported the findings of the PrE0505 trial during the lung cancer oral abstract session at the ASCO20 Virtual Scientific Program. Once a patient had up to six cycles of a combination of durvalumab and chemotherapy, those who had a stable disease, or a partial response could keep going with the durvalumab on the first day of each three week cycle. The most a patient could be administered durvalumab was 12 months. Overall survival rates of the trial were 70.4 percent survival at 12 months and 44.2 percent survival at 24 months.
If eligible for a clinical trial, it may be something useful to look into for those who are victims of mesothelioma, a very rare and aggressive form of cancer that usually affects the lungs.
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Frequently Asked Questions
What was the PrE0505 study?
PrE0505 was a phase 2 clinical trial that tested whether adding the immunotherapy drug durvalumab to standard chemotherapy (pemetrexed and cisplatin) could improve survival in patients with unresectable malignant pleural mesothelioma. The study enrolled 55 patients from 15 cancer centers across the United States between June 2017 and June 2018.
What is durvalumab and how does it work?
Durvalumab is an immunotherapy drug that belongs to a class of treatments called immune checkpoint inhibitors. It works by blocking a protein called PD-L1, which some cancer cells use to hide from the body’s immune system. By blocking this protein, durvalumab helps the immune system recognize and attack mesothelioma cells more effectively. In the PrE0505 study, it was administered once every three weeks alongside chemotherapy.
What were the results of the PrE0505 study?
The results were promising compared to chemotherapy alone:
- Median overall survival: 20.4 months — compared to 12 months for the control group receiving only chemotherapy
- 12-month survival rate: 70.4%
- 24-month survival rate: 44.2%
- Patients with the epithelioid subtype survived longer than two years
These results led researchers to develop a larger phase 3 follow-up trial (PrE0506/DREAM3R) to further test the combination.
What were the side effects reported in the study?
The most commonly reported side effects were anemia, fatigue, and nausea. Treatment-emergent adverse events of grade 3 or higher — meaning more serious side effects — occurred in 65.5% of patients. As with any cancer treatment, the potential benefits must be weighed against the risks, and patients should discuss these with their oncologist.
Who was eligible for the PrE0505 study?
Patients had to meet several criteria to participate, including:
- Over 18 years old with a confirmed diagnosis of unresectable malignant pleural mesothelioma
- Measurable disease visible on CT or MRI imaging
- A minimum of 15 unstained tumor samples available
- ECOG performance status of 0 or 1 (meaning the patient was relatively functional and mobile)
- Adequate organ function
- No prior systemic treatment for mesothelioma
- No participation in another clinical study in the previous four weeks
What is the DREAM3R trial?
Based on the promising results of both the DREAM study and the PrE0505 study, researchers developed a larger follow-up trial called the phase 3 PrE0506/DREAM3R trial. This trial directly compares durvalumab combined with chemotherapy against chemotherapy alone in a larger patient population. It aims to confirm whether the survival benefits seen in the earlier studies hold up in a more rigorous, controlled setting.
What role do clinical trials play in mesothelioma treatment?
Clinical trials are one of the most important ways that new mesothelioma treatments are developed and tested. For patients with limited treatment options — particularly those with advanced or unresectable mesothelioma — clinical trials may provide access to emerging therapies that are not yet widely available. Studies like PrE0505 have helped advance immunotherapy as a treatment option for mesothelioma, offering hope for improved survival rates.
What should I do if I’ve been diagnosed with mesothelioma and want to learn about treatment options?
If you or a loved one has been diagnosed with mesothelioma, understanding the full range of treatment options — including clinical trials — is an important step. Your medical team can help determine whether you may be eligible for current studies. For information about legal options and to request a free Pennsylvania Mesothelioma Information Guide, call (800) 505-6000 or fill out our contact form.
