FDA Lifts Partial Clinical Hold on Pidilizumab

The FDA has lifted its partial clinical hold on the investigational new drug (IND) application for pidilizumab (MDV9300, Medivation, Inc.) in hematologic malignancies and has confirmed that the pivotal phase 2 trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), as well as other studies that cross-reference the IND, may now proceed. The partial clinical hold was not related to any safety concerns.

Medivation has revised the investigator brochure, protocols, and informed-consent documents related to the phase 2 study to reflect the company’s understanding that programmed death-1 (PD-1) is not the target of pidilizumab. No patients have been enrolled in the trial, which began in late 2015. Patients who were receiving pidilizumab through investigator-sponsored studies have continued to receive treatment, and those investigators have been informed to update their protocols and informed-consent documents to state that pidilizumab is not an anti–PD-1 antibody.

The international, open-label trial of pidilizumab is expected to enroll approximately 180 patients with an incomplete response after salvage therapy or autologous stem-cell transplantation for relapsed or refractory CD20-positive DLBCL, transformed indolent lymphoma, or primary mediastinal B-cell lymphoma. The patients will be assessed in two parallel cohorts of approximately 90 patients each. One cohort will consist of patients who have received an autologous stem-cell transplant, and the second cohort will consist of patients who have received salvage chemotherapy but who are ineligible for transplant. Pidilizumab will be administered at a dose of 200 mg by intravenous infusion. The study’s primary endpoint is the best overall response rate.

In 2014, Medivation bought the rights to pidilizumab from CureTech for $335 million, intending to enter the checkpoint-inhibition arena with a drug aimed at PD-1. Recently, however, the company concluded that pidilizumab doesn’t work that way, causing the FDA to red-flag the drug’s pivotal study.

Sources: Medivation; March 9, 2016; and FierceBiotech; January 26, 2016.