This week the first patient enrolled in a multi-center phase I clinical trial of SGN-CD352A for the treatment of patients with relapsed or refractory (r/r) multiple myeloma. SGN-CD352A is an investigational CD352-targeted antibody-drug conjugate (ADC) utilizing Seattle Genetics’ proprietary ADC technology, an engineered cysteine antibody (EC-mAb) stably linked to a highly potent cytotoxic agent called a pyrrolobenzodiazepine (PBD) dimer. [1]
Antibody-drug conjugates are designed to selectively deliver cell-killing agents to tumor cells, and thus may reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.
CD352 is broadly expressed on B-cell cancers including multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, while exhibiting low expression on normal white blood cells. The CD352 engineered cysteine antibody is stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine dimer via site-specific conjugation technology (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the EC-mAb technology allows uniform drug-loading onto an ADC. The ADC is designed to be stable in the bloodstream and to release its potent cell-killing PBD agent upon internalization into CD352-expressing cells.
Multiple Myeloma
Multiple myeloma is a rare and aggressive cancer that forms in white blood cells called plasma cells. Normal, healthy, plasma cells are found in the bone marrow are an important part of the immune system. In contrast, malignant or cancerous plasma cells, which can crowd out healthy blood cells, impair bone strength and weaken the immune system.[2]
The immune system is made up of several types of cells that work together to fight infections and other diseases. Lymphocytes are the main cell type of the immune system – major types of lymphocytes are both T cells and B cells.
Despite recent medical advances, the disease remains an incurable disease in which patients eventually progress and die. Within one year of first-line therapy, 32% of transplant patients and 44% of non-transplant patients relapse. Remission periods are typically shorter for each subsequent line of therapy, with some patients receiving more than four lines of treatment over the course of their disease. After lymphoma and leukemia, multiple myeloma is the third most common blood cancer in the US. According to the World Health Organization, in 2015 more than 124,000 new cases of multiple myeloma were diagnosed worldwide and more than 87,000 people died from the disease. [3]
Trial design
The new clinical trial (NCT02954796) is designed to assess the safety and antitumor activity of SGN-CD352A. This study represents Seattle Genetics’ first clinical-stage ADC program in development for multiple myeloma, demonstrating the breadth of potential therapeutic applications for its industry-leading ADC technology platform.
“More than 124,000 people worldwide are diagnosed annually with multiple myeloma, most relapsing or becoming resistant to current therapies,” noted Robert Lechleider, M.D., Senior Vice President, Clinical Development at Seattle Genetics.
“SGN-CD352A is a novel targeted investigational compound for multiple myeloma, and it is our latest antibody-drug conjugate, or ADC, in an expanding and robust pipeline of clinical stage empowered antibody therapies to address blood cancers and solid tumors. As we begin clinical development of our first compound for multiple myeloma, we continue to explore the broad potential of our ADC technology platform for people with cancer,” Lechleider concluded.
“More than 124,000 people worldwide are diagnosed annually with multiple myeloma, most relapsing or becoming resistant to current therapies”
The phase I, open-label multicenter clinical study is designed to evaluate the safety and preliminary antitumor activity of SGN-CD352A as a single agent in adults with relapsed or refractory multiple myeloma. The trial will be conducted in two parts, with a dose escalation part to identify the maximum tolerated dose of SGN-CD352A followed by an expansion part to further define safety and antitumor activity. SGN-CD352A will be administered every four weeks, and the study will enroll approximately 75 relapsed or refractory patients at multiple centers in the United States.
AACR 2016
Preclinical SGN-CD352A data presented at the 2016 American Association of Cancer Research (AACR) Annual Meeting demonstrated that SGN-CD352A specifically binds to target cells and induces potent antitumor activity in both multiple myeloma and non-Hodgkin lymphoma disease models. In addition to being a potential new monotherapy for multiple myeloma, the tolerability profile from preclinical results suggests that SGN-CD352A may be combined with current standard of care treatments for multiple myeloma.
