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. Craig H. Moskowitz, M.D., Sylvester physician-in-chief, is the principal investigator.
Oncology drug companies have been developing drugs that more effectively hunt down malignant cells and 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. “The drug has been given by itself to well over 100 lymphoma patients and the response rate is greater than 40 percent.”
This study combines ADCT-402 with durvalumab, an immune checkpoint inhibitor to test if, together, there’s an increased response.
Tumors often deceive a patient’s immune system into thinking they are normal tissue, avoiding an immune response. Checkpoint inhibitors tell immune T cells not to be fooled. By inhibiting a protein checkpoint called PD-L1, durvalumab takes the brakes off T cells, allowing them 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 provide a one-two punch against lymphoma, killing cancer cells directly and motivating the immune system to destroy even more. In addition, the combination could act synergistically.
“The concept is that the ADC releases super antigens when it kills cancers, which makes the checkpoint inhibitor much more active,” said Dr. Moskowitz.