MacroGenics reports patient deaths in prostate cancer ADC trial

In an update on its TAMARACK phase 2 clinical trial this week, MacroGenics has reported the deaths of five patients participating in a study evaluating its ADC, vobra duo, in metastatic castration-resistant prostate cancer (mCRPC).

The interim data, updated as of April 12, 2024, includes results from two dosing cohorts of vobra duo: 2.0 mg/kg and 2.7 mg/kg, administered every four weeks. While the study noted some efficacy in terms of prostate-specific antigen (PSA) reduction, significant safety concerns have emerged. While two of the deaths — one from acute myocardial infarction and one from cardiac arrest — were considered unrelated to the study drug by the investigator, the other three deaths, all in the 2.7 mg/kg dosing cohort, are being investigated.

Despite these setbacks, MacroGenics says it remains cautiously optimistic about the potential of vobra duo, particularly due to its targeted action against B7-H3, a protein frequently expressed in various solid tumors. The company is in the initial stages of planning for a possible phase 3 study, pending a thorough analysis of the final TAMARACK trial data, expected in the latter half of 2024.

Vobra duo, or vobramitamab duocarmazine, is an investigational antibody-drug conjugate targeting the B7-H3 protein, which is often overexpressed in various solid tumors. It combines an antibody that binds to B7-H3 on cancer cells with a cytotoxic drug that is released once the complex is internalized by the cancer cell, causing cell death. This targeted mechanism is designed to minimize impact on healthy cells, reducing side effects and improving efficacy. Vobra duo is primarily intended for cancers like mCRPC and potentially other B7-H3 expressing tumors.