Olema Pharmaceuticals, Inc. announced interim results from an ongoing Phase 1b/2 clinical study of OP-1250, the Company's complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD), in combination with palbociclib, a CDK4/6 inhibitor, for the treatment of ER+/HER2- metastatic breast cancer. These results, as of March 8, 2023, were presented in a poster session at the 2023 ESMO Breast Cancer Annual Congress in Berlin, Germany. Across 29 patients, the combination of up to 120 mg of OP-1250 with 125 mg of palbociclib is safe and well-tolerated with no drug-drug interaction (DDI), no induced metabolism of palbociclib, and exposure of both palbociclib and OP-1250 in combination with each other was consistent with the observed monotherapy exposure levels.

No dose-related increases in the incidence, severity, or timing of adverse events were observed, and neutropenia events observed were consistent with the expected profile of palbociclib plus endocrine therapy. Tumor responses and prolonged disease stabilization were observed in this group of patients, including in those previously exposed to palbociclib and other CDK4/6 inhibitors. As of the data cut-off of March 8, 2023, 29 patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer were treated.

In the dose-escalation part, 12 patients were enrolled across four cohorts: three patients per cohort dosed at 30, 60, 90, and 120 mg in combination with palbociclib 125 mg. In the dose-expansion part (ongoing), patients received 120 mg OP-1250 plus palbociclib 125 mg. Seventeen patients had been enrolled in the dose expansion at the time of data cut-off, with a total planned enrollment of approximately 45 patients.

The majority of patients (27 or 93%) were 2/3 line, with 25 (86%) patients having received prior endocrine therapy for advanced disease, 20 (69%) patients having received prior CDK4/6 inhibitors including prior palbociclib, and six (21%) patients having received chemotherapy in the advanced setting. Of 18 patients whose circulating tumor DNA (ctDNA) was assessed as of the data cut-off, 44% had activating mutations in ESR1 at baseline.