Conference Coverage

Early phase 2 data: Mocetinostat/durvalumab combo shows promise in mNSCLC



Combined treatment with mocetinostat and durvalumab shows clinical activity with manageable side effects in patients with metastatic non–small cell lung cancer (mNSCLC) – including patients who progressed on prior checkpoint inhibitor therapy (CIT), according to preliminary findings from a phase 2 trial.

Dr. Manish Patel

Dr. Manish Patel

Of 29 evaluable patients who progressed on prior checkpoint blockade, 12 had “some degree of tumor regression” and 5 achieved a confirmed partial response, Manish Patel, DO, reported at the annual meeting of the Society for Immunotherapy of Cancer.

“Some of these responses were quite durable. The longest response ... was a little over 1 year,” said Dr. Patel, of the University of Minnesota Masonic Cancer Center, Minneapolis.

Several patients continue to show objective responses, and the initial estimate of response duration is a median of more than 5 months, he added.

Of note, no differences have been seen to date with respect to clinical benefit in patients who did and did not have prior clinical benefit on checkpoint blockade, Dr. Patel said.

Overall, the combination was very well tolerated. The most common adverse events were fatigue, nausea, and diarrhea, with more than 10% of patients experiencing grade 3 or higher fatigue.

“Otherwise the toxicities were relatively minor,” he said, noting, however, that 8% of patients had cardiac events during the study, including atrial fibrillation, pericardial effusion, and a few cases of pericardial tamponade.

Such effects have been described in prior mocetinostat monotherapy trials, and all patients in the current study underwent pretreatment echocardiograms and did not have evidence of pericardial effusion at the start.

“So I think this is likely to be related to mocetinostat,” Dr. Patel said.

Mocetinostat is a spectrum-selective class I and class IV histone deacetylase inhibitor with multiple potential immunomodulatory features.

For example, the agent induces major histocompatibility complex Class I and Class II expression on tumor cells, enhances the function of T effector cells, and decreases the function of immunosuppressive cell subsets, including regulatory T cells and myeloid derived suppressor cells, Dr. Patel noted.

“It was hypothesized that because of these pleiotropic immune-supportive effects, that the combination of mocetinostat and checkpoint blockade might be a successful strategy for patients with non–small cell lung cancer,” he said.

In phase 1, doses of 50 mg, 70 mg, or 90 mg given three times weekly in combination with 1,500 mg of durvalumab were studied in patients with advanced solid tumors. Based on the safety data from that phase of the study, the recommended phase 2 dose of mocetinostat was 70 mg three times weekly with 1,500 mg of durvalumab on day 1 of each 28-day cycle.

Study subjects were patients with mNSCLC who had received at least one platinum-based doublet and whose most recent treatment prior to enrollment was with a checkpoint inhibitor, or who were immunotherapy naive.

The findings show promising clinical efficacy and safety, and enrollment in the study, which began in June 2016, is currently ongoing in the United States, he said.

Dr. Patel is an advisory board member for Nektar Therapeutics and has received research funding from Merck.

SOURCE: Patel M et al. SITC 2018, Abstract 027.

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