Adding Imfinzi (generic: durvalumab) to chemotherapy improves survival for diagnosed with inoperable malignant pleural mesothelioma, according to recent data from a Phase 2 clinical trial.
The clinical study is the first to show cancer patient survival times going over 20 months in this patient population. A Phase 3 trial – DREAM3R – to confirm the combination’s effectiveness over just chemotherapy will open in September 2020.
The Phase 3 trial will enroll patients at sites that have not been announced yet in the US and Australia in late 2020.
Findings on the effectiveness of Imfinzi with chemo were delivered in this presentation: PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM), at the 2020 American Society of Clinical Oncology Virtual Scientific Program.
The drug plus standard chemo provided a promising median survival rate for patients who had untreated, inoperable malignant pleural mesothelioma, stated Patrick Forde, MD. Ford is a professor of oncology at Johns Hopkins University School of Medicine.
Mesothelioma Patients Usually Treated With Chemotherapy, Radiotherapy, and Surgery
Pleural mesothelioma is rare cancer caused by asbestos exposure that grows on the protective tissue that covers the lungs.
Imfinzi is an immune checkpoint inhibitor that was developed by AstraZeneca. It targets and blocks the PD-1 receptor in immune T-cells. This prevents it from interacting with PD-L1, in cells with cancer.
Because this interaction is part of what is used by cancer cells to get around the immune system, it is believed that Imfinzi can improve anti-tumor responses.
Clinical studies have shown good results with PD-1 blockade therapies in patients with pleural mesothelioma. Also, the PD-1/PD-L1 pathway causes inflammation, which plays a significant role in the growth of mesothelioma tumors.
Clinical Study Involves 60 Adults Diagnosed With Inoperable Mesothelioma
Based on the above findings, the PRECOG cancer research group, working with AstraZeneca, started the PRE0505 2 trial to study the potential benefits of adding Imfinzi to chemotherapy in 60 adults diagnosed with pleural mesothelioma that is inoperable.
The participants had a median age of 68 and were recruited at 15 sites in the US from 2017 to 2018. Most were men and had the epithelioid type of mesothelioma, which is most frequent in pleural mesothelioma forms of the disease. It is also the most treatable.
All clinical trial participants received Imfinzi and standard chemotherapy -Alimta and carboplatin or cisplatin – every 21 days for as many as six cycles. This was followed by a year of Imfinzi treatment in those showing signs of disease.
The main goal of the clinical trial was to check whether this combination therapy improved survival rates. The other goals were to see how long patients lived without signs of cancer progression, the response rate, and safety measures.
Results Showed That Trial Met Its Goal of Longer Survivability
After a follow-up of approximately 20.6 months, trial results showed that it had met its goal. Patients on the combo therapy lived longer – a median of 20.4 months – than a historical group of patients given just chemotherapy; they lived a median of 12.1 months.
Approximately 87% of trial participants were alive after six months, 70% at one year, and 44% at two years. They lived without any signs of disease progression for 6.7 months; 69% had no disease progression at six months, 16.5% at one year, and 10.9% at two years.
Also, 56.4% achieved partial response, 40% showed stable disease, and one patient had their disease progress.
During their exploratory analyses, researchers did not find a major link between tumor PD-L1 levels or tumor mutational burden and patient survival or rates of disease progression.
Overall, the combination therapy was tolerated well by patients and there were no significant toxicities. Most adverse events involving Imfinzi were mild.
Previous Phase 2 Trial in Australia Showed Similar Results
A similar Phase 2 trial is Australia called DREAM showed that nearly 50% of patients responded to combination therapy. Also, 57% of patients had no disease progression at six months.
Researchers said that the trial’s favorable data showed they should move forward with a Phase 3 trial.
The future DREAM3R Phase 3 trial will be led by PrECOG and the University of Sydney, as well as AstraZeneca. The trial is believed to be enrolling 280 adults with untreated, inoperable malignant pleural mesothelioma.
Those who enroll in the study will be assigned to Imfinzi combined with standard chemotherapy, or to just chemotherapy for four to six cycles. People in the combination group will get maintenance therapy with Imfinzi until there is excessive toxicity, patient withdrawal, or disease progression.
- Imfinzi Plus Chemo Aids Survival in Inoperable Pleural Mesothelioma, Phase 2 Data Show. Accessed at https://immuno-oncologynews.com/2020/07/20/imfinzi-plus-chemo-aids-survival-in-inoperable-pleural-mesothelioma-phase-2-data-show/