MacroGenics reports deaths in prostate cancer trial

MacroGenics has provided an update on its TAMARACK phase 2 clinical trial, revealing the deaths of five patients involved in the study of its antibody-drug conjugate (ADC), vobra duo, for metastatic castration-resistant prostate cancer (mCRPC). This experimental treatment is under investigation for its effectiveness and safety in treating advanced prostate cancer that has not responded to other forms of therapy.

As of the latest interim data, updated on April 12, 2024, the study has been examining the outcomes of two different dosing levels of vobra duo: 2.0 mg/kg and 2.7 mg/kg, administered once every four weeks. The findings have shown some promising signs in terms of reducing prostate-specific antigen (PSA) levels, a marker commonly used to assess the presence and progression of prostate cancer. However, significant safety concerns have arisen during the trial.

Among the five reported deaths, two were deemed unrelated to the study drug. One patient suffered from acute myocardial infarction, and another experienced cardiac arrest. These were not attributed to the administration of vobra duo by the study's investigator. On the other hand, the remaining three deaths, which occurred within the 2.7 mg/kg dosing group, are currently under investigation to determine any possible connection to the drug.

Despite these unfortunate events, MacroGenics maintains a cautious optimism regarding the future of vobra duo. The company highlights the potential of the drug due to its targeted mechanism of action against the B7-H3 protein. This protein is known to be frequently expressed in various solid tumors, making it a promising target for cancer treatment. MacroGenics is in the early stages of planning a phase 3 trial, which will depend on a comprehensive analysis of the final data from the TAMARACK trial, expected in the latter half of 2024.

Vobra duo, also known as vobramitamab duocarmazine, is an investigational treatment designed to selectively target cancer cells while sparing healthy tissue. It functions by combining an antibody that specifically binds to the B7-H3 protein on cancer cells with a cytotoxic drug. This drug is released once the antibody-drug complex is internalized by the cancer cell, leading to cell death. This targeted approach aims to reduce side effects typically associated with conventional chemotherapy and enhance the efficacy of the treatment.

The development of vobra duo is particularly significant for patients with mCRPC, a challenging form of prostate cancer that has limited treatment options after initial therapies have failed. Furthermore, the potential application of vobra duo extends beyond prostate cancer, as B7-H3 is overexpressed in a variety of other solid tumors. This broad spectrum of applicability underscores the importance of continued research and development in this area.

MacroGenics' commitment to advancing vobra duo, despite the challenges encountered, reflects the ongoing need to find effective and safer treatments for cancer patients. The upcoming detailed analysis of the TAMARACK trial's final data will be crucial in determining the viability of moving forward to a phase 3 study and ultimately bringing this promising therapy closer to those in need.