ESMO: It's early days for Pfizer's EZH2 inhibitor, but there's a glimpse of hope for some

EZH2 inhibitors are a budding drug class—already with one approved therapy and a few in the pipeline—and Pfizer is the largest pharma to add the tool to its clinical belt. And phase 1 data of Pfizer's asset point toward a positive safety profile, with glimpses of benefit for some cancer patients, though not all tested may be able to count on the therapy. 

The results, presented Sunday at the European Society of Medical Oncology (EMSO) congress 2022, are admittedly a very early peek under the hood of the company's EZH2 inhibitor in a trial that was mainly focused on nailing a dose and maximizing tolerability.

The med at play, PF-06821497, was aimed at follicular lymphoma, castration-resistant prostate cancer (CRPC) and small cell lung cancer in this initial study. And the trial was broken up into two parts: one testing the med solo, given twice daily in escalating doses in all three diseases, and a second looking at PF-06821497 as part of a combo only in prostate cancer. 

Out of 15 evaluable follicular lymphoma patients, four had a partial response. In CRPC, two out of eight had stable disease. But the two patients with small cell lung cancer both showed disease progression, a small sample size but foreboding nonetheless.

In the prostate-cancer-focused portion, patients were previously treated with Zytiga and/or androgen deprivation therapy. In the study, they received Xtandi and an androgen deprivation therapy on top of PF-06821497 given at the highest 1,250-mg dose used in the dose-escalation group. An objective response was seen in four out of 28 patients, and 10 had stable disease. Among 57 total patients, there was one treatment-related adverse event, with a single patient reporting a dose-limiting toxicity of grade 4 low platelet count. 

The ESMO data mark the first look from Pfizer in this new class of therapies, which may been gaining traction. Epizyme won an approval for its EZH2 inhibitor in 2020, and, this June, Ipsen bought the company for $247 million. The drug's approved for follicular lymphoma and epithelioid sarcoma.

And a few other EZH2 inhibitors are coming down the clinical trial pike, including from German-based Morphosys as well as China-based Jiangsu Hengrui Medicine. 

EZH2 is part of a family of genes that repress transcription and play a major function in cell cycle progression. As a result, its role in disease progression at-large, including cancer, has become a focal point. Should EZH2 function go a bit haywire, cells may be able to survive past their due date, prompting cancer development. 

As for Pfizer’s trial, recruitment is ongoing. The early look shown was from a data cutoff from nearly a year ago, in September 2021, and, according to the clinical trial record, the company expects to recruit 185 patients.