Adoptive T-cell therapy ADP-A2M4 targeting MAGE-A4 shows early activity in patients with advanced solid tumors
MD Anderson-led Phase I trial of Adaptimmune T-cell receptor therapy sees confirmed responses in multiple cancer types
MD Anderson News Release May 29, 2020
ABSTRACT: #
The adoptive T-cell therapy ADP-A2M4, which is engineered to express a T-cell receptor (TCR) directed against the MAGE-A4 cancer antigen, achieved responses in patients with multiple solid tumor types, including #102synovial sarcoma, head and neck cancer and lung cancer, according to results from a Phase I clinical trial led by researchers at .
Among 38 patients treated on the trial, the ADP-A2M4 T cells resulted in overall response (OR), or tumor shrinkage, in 9 patients (23.7%) and stable disease in 18 patients (47.4%). Trial data were shared in an oral presentation at the by principal investigator , professor of Investigational Cancer Therapeutics.
¡°Thus far, we haven¡¯t seen strong responses in treating solid tumors with available cellular therapies, in large part because antigens expressed are not restricted to the tumors,¡± said Hong. ¡°In this trial, I¡¯ve been encouraged to see durable responses in several patients, and the results suggest there is potential for this emerging TCR-based technology for treating solid tumors.¡±
Adoptive cellular therapy is a form of immunotherapy that modifies immune cells to be more effective in mounting an immune response against cancer. For ADP-A2M4, T cells are isolated from patients and engineered to express a TCR targeting MAGE-A4, a protein normally expressed only in the testis but present in certain cancers.
Unlike chimeric antigen receptor (CAR)-modified T cells, which target surface proteins on cancer cells, TCR T-cell therapies are able to target proteins normally found inside the cell by recognizing protein fragments bound to immune-related proteins on the cell surface.
The was designed as a dose-escalation study to assess the safety, tolerability and antitumor activity of ADP-A2M4 in patients with advanced solid tumors with expression of the MAGE-A4 protein. Patients on the trial included those with synovial sarcoma, ovarian cancer, head and neck cancer, gastric cancer, myxoid/round cell liposarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer and melanoma. Participants had a median of three prior lines of systemic therapy.
The therapy achieved strong responses in particular groups of patients in the trial. Patients with synovial sarcoma saw a 43.8% OR rate and a disease control rate of more than 90%. There also was an additional patient with an unconfirmed response after the data cut-off. Median duration of response in these patients was 28 weeks and median progression-free survival was 20 weeks. Confirmed responses were also seen in patients with lung cancer and head and neck cancer.
Most patients (97.4%) experienced some treatment-related adverse events, with the most common being low blood cell counts (lymphopenia, leukopenia, neutropenia, anemia and thrombocytopenia). Half of patients experienced cytokine release syndrome. Two patients had trial-related deaths, which led to modification of the lymphodepletion regimen and eligibility criteria.
¡°The side effects seen on the trial were largely consistent with those typically experienced by cancer patients undergoing lymphodepleting chemotherapy and cellular therapy,¡± said Hong. ¡°This study is a nice proof of concept for treating solid tumors and suggests there could be a role for cellular therapies in these indications going forward.¡±
This research is part of an ongoing strategic alliance between MD Anderson and Adaptimmune, designed to expedite the development of novel T-cell therapies for multiple cancer types. Translational research and analyses of related biomarkers continues. Results from this study led to a low-dose radiation sub-study, a of ADP-A2M4 in sarcoma and a of Adaptimmune¡¯s next-generation T-cell therapy targeting MAGE-A4, ADP-A2M4CD8.
This study was funded by Adaptimmune. A full list of co-authors and their disclosures can be found .