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.