Imfinzi Plus Chemo Aids Survival in Inoperable Pleural Mesothelioma, Phase 2 Data Show

Imfinzi Plus Chemo Aids Survival in Inoperable Pleural Mesothelioma, Phase 2 Data Show
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Adding Imfinzi (durvalumab) to standard first-line chemotherapy prolongs survival for adults newly diagnosed with inoperable malignant pleural mesothelioma, according to data from a Phase 2 clinical trial.

This study is the first to show survival times exceeding 20 months in this patient population. A Phase 3 trial, called DREAM3R (NCT04334759), to confirm the combination’s superiority over chemotherapy alone is set to open in September.

It will enroll patients at sites, yet to be announced, in the U.S. and Australia later this year. Contact information for this study can be found here.

Findings were in the 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) — A PrECOG LLC study,” given at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

“[Imfinzi] plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma,” Patrick Forde, MD, who presented the data, said in an ASCO news release.

Forde is an associate professor of oncology at Johns Hopkins University School of Medicine, in Baltimore, and the director of the Kimmel Center’s thoracic cancer clinical research program.

Malignant pleural mesothelioma is a rare cancer, commonly linked to asbestos exposure, that forms on the thin protective tissues that cover the lungs — the pleura.

Patients are often treated with a combination of chemotherapy, radiotherapy, and surgery. However, this usually leads to only minor improvements in survival outcomes.

Imfinzi, an immune checkpoint inhibitor developed by AstraZeneca, targets and blocks the activity of the PD-1 receptor in immune T-cells, preventing its interaction with PD-L1 in cancer cells.

Since this interaction is part of a mechanism frequently used by cancer cells to evade the immune system, Imfinzi is expected to boost anti-tumor responses.

Studies have shown positive results with PD-1 blockade therapies in patients previously treated for malignant pleural mesothelioma. In addition, the PD-1/PD-L1 pathway is also involved in inflammation, which plays a key role in the development of pleural mesothelioma.

Based on these findings, the U.S.-based PrECOG cancer research group, in collaboration with AstraZeneca, launched the PrE0505 Phase 2 trial (NCT02899195) to evaluate the benefits of adding Imfinzi to standard chemotherapy in 55 adults newly diagnosed with inoperable malignant pleural mesothelioma.

Participants, with a median age of 68, were recruited at 15 U.S. sites between 2017 and 2018. Most were men (81.8%) and had the epithelioid cancer subtype (75%), the most common in pleural mesothelioma cases.

All were given a combination of Imfinzi and standard chemotherapy — Alimta (pemetrexed) and cisplatin or carboplatin — every three weeks for up to six cycles, followed by up to one year of Imfinzi maintenance treatment in those showing at least stable disease.

The trial’s main goal was to assess whether the combination therapy improved patients’ overall survival. Secondary goals included the time patients lived without signs of disease progression, the objective response rate (the proportion of patients with partial and complete responses), and safety measures.

After a median follow-up of 20.6 months, results showed that the trial met its primary goal, with patients on the combination therapy living significantly longer (median of 20.4 months) than an historical group of patients given standard chemotherapy alone (12.1 months).

A total of 87.2% of trial participants were alive at six months, 70.4% at one year, and 44.2% at two years. They lived without signs of disease progression for a median of 6.7 months; 69.1% were free from disease progression at six months, 16.4% at one year, and 10.9% at two years.

In addition, more than half (56.4%) achieved a partial response, 40% showed stable disease, and one patient had disease progression.

In exploratory analyses, researchers found no significant links between tumor PD-L1 levels or tumor mutational burden and patient survival or disease progression rates.

The combination therapy was well tolerated, with no unexpected toxicities.  Most Imfinzi-related adverse events were mild in severity.

A previous, similar Phase 2 trial held in Australia, called DREAM (ACTRN12616001170415), showed (abstract OA08.02) that almost half of the patients responded to the combination therapy, and 57% were free from disease progression at six months.

Overall, the trial’s data “signal us to move forward with a Phase 3 study,” Forde said.

The upcoming DREAM3R Phase 3 trial is being led jointly by PrECOG and the University of Sydney, in collaboration with AstraZeneca. It is expected to enroll 280 adults with previously untreated, inoperable malignant pleural mesothelioma.

Those enrolled will be randomly assigned to either Imfinzi in combination with standard chemotherapy, or to chemotherapy alone for four to six cycles. Those in the combination therapy group will continue maintenance therapy with Imfinzi until disease progression, unacceptable toxicity, or patient withdrawal.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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