Tremelimumab, Imfinzi Combo Has Manageable Side Effects in Mesothelioma, Italian Trial Shows

Tremelimumab, Imfinzi Combo Has Manageable Side Effects in Mesothelioma, Italian Trial Shows

It is safe for malignant mesothelioma patients to combine Tremelimumab and Imfinzi (durvalumab), according to a study to be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, set for June 2-6 in Chicago.

Forty patients had received the combo treatment in the open-label Phase 2 trial (NCT02588131) and adverse events among them were mostly reversible, though three patients quit the treatment because of side effects.

Researchers at Italy’s University Hospital of Siena conducted the trial, Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study. It was sponsored by the Italian Network for Tumor Biotherapy Foundation in collaboration with  AstraZeneca, developer of both drugs.

Participants received 1 mg/kg intravenous tremelimumab, every four weeks, for a total of four doses, and 13 doses of 20 mg/kg intravenous Imfinzi, given every four weeks.

The group consisted of 38 patients with pleural mesothelioma, and two patients with peritoneal cancer. Among them, 12 received the treatment as their first mesothelioma therapy, while 28 had been through one previous treatment round. They were on average 64 years old and in relatively good physical health.

Up to January 2017, they had received a median 5.5 doses of therapy, with 60 percent of the group experiencing immune-related adverse events. Five patients, or 12.5 percent, experienced more severe events of grade 3 or 4 — the most common being liver toxicity. Of the three patients who quit treatment, one had a low platelet count, one developed a brain inflammatory condition, and one had severe liver toxicity.

Both tremelimumab and Imfinzi are so-called immune checkpoint inhibitors. The drugs act by releasing the brakes applied on the immune system by the tumor. In other cancer types, checkpoint blockers have been linked to very good responses. But mesothelioma trials have, so far, not been convincing.

Tremelimumab targets the checkpoint molecule CTLA4, while Imfinzi blocks a molecule called PD-L1. Earlier studies have suggested that the two drugs might work better when given together. As a result, several ongoing trials are exploring that combination in mesothelioma.

The study will run until March 2018. Overall survival data — one of the study’s many secondary outcome measures — will be assessed after 120 weeks.

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