Conference Coverage

HDAC inhibition may boost immune therapy efficacy in breast cancer

 

Key clinical point: Entinostat and nivolumab with or without ipilimumab shows promise in advanced breast cancer.

Major finding: Three patients had a partial response, 12 had stable disease, 5 progressed.

Study details: A phase 1 dose-expansion study involving 30 patients.

Disclosures: This study was funded by grants from the National Institutes of Health, Bloomberg Kimmel Institute for Immunotherapy, NCCN, and the Mary Kay Foundation, and by a V Foundation award. Dr. Connolly reported having no disclosures.

Source: Connolly RM et al. NCCN, Poster 3.


 

REPORTING FROM THE NCCN ANNUAL CONFERENCE

– The novel combination of entinostat and nivolumab with or without ipilimumab showed encouraging safety, tolerability, and antitumor activity in early results from an ongoing phase 1 trial of patients with advanced breast cancer.

Of 30 patients who were enrolled and treated in the dose-escalation phase of the study as of Feb. 24, 2018, 20 had evaluable responses, and of those, 3 had a partial response for an overall response rate of 15%. An additional 12 had stable disease, and 5 had disease progression, Roisin M. Connolly, MD, reported in a poster at the annual conference of the National Comprehensive Cancer Network.

Sharon Worcester/MDedge News

Dr. Roisin Connolly

All patients received 5 mg of entinostat during a 2-week run-in period. After that, dose level 1 (DL1) patients received 3 mg of entinostat weekly plus 3 mg/kg of nivolumab every 2 weeks, dose level 2 (DL2) patients received 5 mg of entinostat weekly and 3 mg/kg of nivolumab every 2 weeks, dose level 3 (DL3) patients received 3 mg of entinostat weekly plus 3 mg/kg nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks for up to four doses, and dose level 4 (DL4) patients received 5 mg of entinostat weekly plus 3 gm/kg nivolumab every 2 weeks and 1 mg/kg of ipilimumab every 6 weeks for up to four doses.

Responses were seen in all 3 DL1 patients, 12 of 14 DL2 patients, 3 of 4 DL3 patients, and 2 of 9 (with 4 pending first restaging) DL4 patients. Dose-limiting toxicities included one case of pneumonitis at DL2 and an allergic reaction in one DL4 patient, said Dr. Connolly of Johns Hopkins University, Baltimore.

The most common treatment-associated adverse events occurring in 6 or more patients included anemia, fatigue, neutropenia, nausea, and rash, with each occurring in 12 to 22 patients, including grade 3 anemia in 7 patients, grade 3 fatigue in 4 patients, and grade 3 neutropenia in 5 patients. Grade 4 adverse events included lymphopenia in one patient and elevated lipase in one patient, she said.

Possible immune-related adverse events included hypothyroidism in 2 DL2 patients and 3 DL3 patients, hyperthyroidism in 1 DL3 patient, colitis in 1 DL2 and 1 DL3 patient, pneumonitis in 4 DL2 patients, rash in 10 DL2-DL4 patients, and meningoencephalitis and myasthenia gravis in 1 DL3 patient.

Study participants were adults with a mean age of 60 years with metastatic or unresectable solid tumors for which standard treatments did not exist or were no longer effective, or for which treatment with anti–programmed cell death ligand1/cytotoxic T-lymphocyte antigen 4 treatment was appropriate. All had good performance status and adequate organ and pulmonary function, less than 30% liver involvement, and any brain metastases were stable. Those with active autoimmune disease or a history of autoimmune disease that might recur were excluded, as were patients treated within 14 days of enrollment.

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