PIKAMAB, a stratified medicine biopharmaceutical company, announced today that it is developing ADCC TherasightTM, a novel theragnostic product that can help guide the drug development process and patient treatment protocols for the cancer therapeutic antibodies that use ADCC (antibody-dependent cellular cytotoxicity) as the major mechanism of action.
ADCC Therasight uses PIKAMAB’s proprietary stratification method, 3x3 MatrixTM, to measure the ADCC profile of patients by stratifying them into nine distinct groups. This involves two-dimensional stratification of the functional polymorphisms present in two key receptors, FcGR-3A and FcGR-2A. These receptors expressed on immune effector cells are responsible for binding to therapeutic antibodies and mediate killing of cancer cells by a process called ADCC.
Ronald Levy, M.D., at Stanford University School of Medicine provided clinical evidence that both FcGR-2A and FcGR-3A receptors dictate the therapeutic response rate of B-cell non-Hodgkin’s lymphoma (B-NHL) patients to rituximab treatment. This was based on a well defined, retrospective analysis of patient samples from B-NHL patients who were treated with rituximab as a monotherapy (no chemotherapy or radiation therapy involved) and followed for over 10 years. According to this study, ~4% of the patients were excellent responders with longer progression-free survival, ~30% were moderate responders, and ~65% were poor responders with shorter remissions.
Rituximab uses ADCC as the major mechanism of action in B-NHL indication. “Out of ~200 or so antibodies in the drug development pipeline, a significant number of antibodies are expected to use ADCC as a primary mechanism of action, and you can see this relatedness in sufficiently powered clinical studies when ADCC Therasight is used,” said Vijay Ramakrishnan, Ph.D., CEO of PIKAMAB.
ADCC Therasight could identify responders and non-responders prior to the administration of rituximab in B-NHL patients. The Company plans to develop a CLIA-certifiable test to enable physicians and payers to incorporate ADCC Therasight as part of their routine patient treatment protocols.
Not all patients treated with trastuzumab (indication: breast cancer) and cetuximab (indication: metastatic colorectal cancer) respond well even when the patients are selected based on their Her-2 expression profile or K-RAS genetic profile, respectively. This is because ADCC plays an equally important role in providing therapeutic response. “We can potentially treat more patients (from the currently ‘non-treatable’ group) when ADCC Therasight is used in conjunction with Her-2 and K-RAS tests,” explained Ramakrishnan.