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The anti-PD-1 monoclonal antibody TSR-042 may be safe and effective for the treatment of patients with microsatellite-high (MSI-H) endometrial cancer.
The anti-PD-1 monoclonal antibody TSR-042 appeared to be safe and effective in the treatment of patients with microsatellite-high (MSI-H) endometrial cancer, according to preliminary results presented at the European Society for Medical Oncology (ESMO)’s 2018 Congress.
PD-1, a protein found on T cells (a type of immune cell) that helps keep the body's immune responses in check, is a key immune checkpoint molecule that can limit T-cell-mediated immune responses in patients with cancer. When PD-1 is bound to another protein, PD-L1, it helps to keep T cells from killing other cells, including cancer cells.
Therefore, blocking PD-1 has been shown to boost antitumor immune responses and to increase survival of patients with multiple tumor types, the researchers wrote.
Meanwhile, MSI-H status affects how a patient may respond to treatment: The immune system is more easily able to “recognize” MSI-H tumors, meaning that they respond far more readily to immunotherapy drugs, like TSR-042.
The ongoing GARNET trial — a multicenter, open-label, Phase 1 dose-escalation study – is designed to evaluate the safety and efficacy of TSR-042 monotherapy in patients with advanced solid tumors.
A weight-based dose escalation study (part 1) and a fixed-dose safety study (part 2A) were previously completed to determine the recommended phase 2 dose. Now, the study is enrolling patients with specific tumor types into four expansion cohorts (part 2B), including endometrial cancer and non-small cell lung cancer.
At ESMO — held in Munich, Germany, from Oct. 19-23 – the researchers presented a poster that focused specifically on the portion of the study that examined the effects of the recommended phase 2 dose in patients with previously treated recurrent or advanced MSI-H endometrial cancer that had received no more than two lines of previous therapy.
Efficacy endpoints included the objective response rate, duration of response, and duration of response per the immune-related Response Evaluation Criteria in Solid Tumors which were assessed by the researchers.
Currently, 35 patients are enrolled in the MSI-H endometrial cancer cohort and received TSR-042 at the recommended phase 2 dose of 500 mg every three weeks for four doses, then 1000 mg every six weeks until disease progression.
On average, patients were approximately 63 years old and the majority (74 percent) had endometrioid carcinoma.
All-grade side effects that emerged after treatment started occurred in 32 patients, of which grade 3 or higher side effects like this occurred in 13 people, including two caused from treatment itself — aspartate aminotransferase (an enzyme involved in the balance of proteins) levels increased and fever. No treatment-related death was reported.
The most common side effects that occurred after treatment started included diarrhea (20 percent) and fatigue (14.3 percent).
At data cutoff for the preliminary results, 25 patients had one or more tumor assessment or discontinued treatment prior to their first assessment. Of those who remained, the overall response rate was 52 percent, including one patient with an unconfirmed partial response who is still currently enrolled in the study. Twelve responses are ongoing, including three patients with a partial response have been receiving TSR-042 for more than 60 weeks. Duration of response has not been reached.
The preliminary efficacy and safety data detailed in these results indicate that TSR-042 is safe and well-tolerated and performs much like other approved PD-1 inhibitors.
“Preliminary efficacy data indicates robust activity of TSR-042 in MSI-H (endometrial cancer) patients with previously platinum-treated advanced disease,” the researchers wrote. “Preliminary safety findings indicate that TSR-042 is safe and well tolerated, with a profile characteristic of approved PD-1 inhibitors.”