New Trial Delivers One-Two Punch to Aggressive Lymphomas

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An innovative drug combination is now being tested in a Phase 1 clinical trial for patients with advanced non-Hodgkin lymphoma, when standard treatments have failed. Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine is one of the sites for this trial, with Sylvester Physician-in-Chief Craig Moskowitz, M.D., serving as principal investigator.

Moskowitz
Craig Moskowitz, M.D., physician-in-chief at Sylvester Comprehensive Cancer Center

Oncology drug companies have been developing drugs that more effectively hunt down malignant cells and then, in clinical studies such as this one, combining them with other treatments to cut off cancer’s “escape routes.”

One of these new targeted therapies is an antibody drug conjugate (ADC) called ADCT-402. Developed by ADC Therapeutics, ADCT-402 harnesses the homing action of antibodies with the anti-cancer toxicity of a chemotherapeutic. The antibody attaches itself to a protein commonly found in B cells called CD19. Once they bind, the payload – a drug called PBD – is internalized by the cancer cell. PBD is designed to disrupt DNA and kill the cell.

“This is the second generation of antibody drug conjugates,” Dr. Moskowitz said. “ADCT-402 has been given by itself to well over 100 lymphoma patients, and the response rate is greater than 40 percent.”

But that may just be the start. By combining different agents, oncologists and drug companies hope to increase their efficacy against tumors. In this case, Sylvester has been enlisted to test ADCT-402 in combination with durvalumab, an immune checkpoint inhibitor.

Tumors often deceive a patient’s immune system into thinking they are normal tissue, thwarting an immune response. Checkpoint inhibitors tell immune T cells not to be fooled. By inhibiting a protein checkpoint called PD-L1, durvalumab allows T cells to attack the cancer.

“The people in this study are some of the sickest cancer patients, having already been treated with anti-cancer drugs that are no longer or were never effective,” Dr. Moskowitz said.

The hope is that these two therapies will kill lymphoma cells directly and motivate the immune system to destroy even more. The combination could also act synergistically with even greater efficacy, Dr. Moskowitz said.

“The concept is that the ADC releases super antigens when it kills cancers, which makes the checkpoint inhibitor much more active.”

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