AstraZeneca recently announced that the Phase 2b clinical trial evaluating tremelimumab monotherapy for the treatment of patients with unresectable malignant mesothelioma —the DETERMINE study — did not meet its primary endpoint of improving overall survival.
Tremelimumab was developed by AstraZeneca and its global biologics research and development arm, MedImmune, as a second- or third-line treatment for mesothelioma. It is a human antibody binding to, and blocking, CTLA-4, a molecule hindering immune T-cell activation. By blocking the activity of CTLA-4, tremelimumab boosts the immune response against cancer cells. Tremelimumab has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA).
The drug is currently being investigated as a monotherapy in mesothelioma patients, and in combination with another investigational drug from Astra-Zeneca – durvalumab (MEDI473) – as a treatment for multiple non-mesothelioma cancer types, such as bladder, head and neck, gastric, pancreatic, liver, and blood cancers. The tremelimumab and durvalumab combination is also being investigated in two clinical trials for malignant mesothelioma (NCT02588131 and NCT02592551).
A recently released study showed promising results of the combination therapy in patients with locally advanced or metastatic non-small cell lung cancer.
The DETERMINE trial is an international, multicenter study evaluating the efficacy and safety of tremelimumab in 571 patients with unresectable malignant mesothelioma in the lining of the lungs or abdomen.
In the company press release, Robert Iannone, senior vice president and head of Immuno-Oncology, Global Medicines Development, at AstraZeneca, said: “We are disappointed that tremelimumab monotherapy did not demonstrate a survival benefit in this patient population with no approved medicines beyond first-line treatment. However, we remain confident in tremelimumab’s clinical activity in combination, as shown in our recently published Study 006 trial of tremelimumab and durvalumab in non-small cell lung cancer.”
The release gave no mention of data on any of the secondary outcomes of the trial, including measures of treatment response and the length of progression-free survival. It also did not comment on safety aspects or adverse events during the trial.
AstraZeneca will complete a full evaluation of final data from the DETERMINE trial, and plans to present the data at a medical meeting later this year, the company said in its release.