TCR T-Cell Therapy Shows Efficacy Across MAGE-A4+ Solid Tumors
ADP-A2M4CD8 will be evaluated in the phase 2 SURPASS-3 trial initiating in late 2022 or early 2023.
ADP-A2M4CD8, a CD8+ T-cell receptor (TCR) engineered T-cell therapy has yielded responses across a variety of MAGE-A4+ solid tumors, including ovarian, urothelial, gastroesophageal, and head and neck cancers.1
These data, from the phase 1 SURPASS trial (NCT04044859), were presented at the European Society for Medical Oncology Congress 2022, September 9-13, in Paris, France, by David S. Hong, MD, professor and deputy chair, department of investigational cancer therapeutics, MD Anderson Cancer Center, The University of Texas.
"I'm encouraged by the responses we've seen thus far in multiple solid tumor types during the SURPASS signal-finding trial, and I look forward to seeing data from future clinical studies,” Hong said in a statement.2 "This is an important and exciting time in oncology with TCR T-cell therapies, such as afami-cel and the next-gen CD8 therapy, and their potential to help clinicians manage aggressive and difficult-to-treat cancers."
Hong presented data from 43 evaluable patients as of the data cutoff date of August 1, 2022, 13 with ovarian cancer, 12 with gastroesophageal cancer, 7 with urothelial cancer, and 4 with head and neck cancer. Patients were heavily pre-treated, with a median 3 prior lines of therapy (range, 1-8).1
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Hong and colleagues found that the overall response rate (ORR) in all participants was 33% , the disease control rate (DCR) was 81%, and the median duration of response (DOR) was 12 weeks (range, 7-over 65). Restricting analyses to participants with ovarian, urothelial, and head and neck cancers yielded an ORR of 44%.
Specifically, participants with ovarian cancer had an 86% DCR (n = 12), with 5 partial responses (PR; 36%) and 1 CR. Participants with urothelial cancer mostly had reductions in target lesions (n = 6), 3 had PRs, and there was 1 unconfirmed response after the cutoff date. Three participants with head and neck cancer had partial responses. One participant with gastroesophageal cancer had a confirmed response and 1 had an unconfirmed response that was confirmed after data cutoff. DCR was 77%.
"Our SURPASS signal-finding trial continues to be a great success," Adrian Rawcliffe, chief executive officer, Adaptimmune, added to the statement.2 "We are seeing robust levels of clinical response in heavily pre-treated people with late-stage cancers expressing MAGE-4, independent of tumor type. Our product candidate has been well tolerated and it is abundantly clear that this next gen CD8 TCR T-cell can effectively target solid tumors and is markedly more potent than our first-gen product in tumors outside of sarcoma. With these results, we have the opportunity to convert signals of efficacy into products for multiple cancer indications, such as ovarian, gastroesophageal, urothelial, and head & neck cancers which are large populations with high unmet medical need. We are thankful to both the dedicated clinical trial participants and their caregivers, for their commitment to helping us develop and deliver innovative cancer therapies."
ADP-A2M4CD8 had a manageable safety profile consistent with chemotherapy, immunotherapy, and/or cell therapy. There were 2 deaths related to treatment, 1 due to pneumonia and cytokine release syndrome (CRS) and the other due to bone marrow failure with a history of chronic anemia. Most participants (73%) experienced CRS of grade 2 at most (86%). Cytopenia of at least grade 3 (25%) and immune effector cell-associated neurotoxicity Syndrome (7%) related to treatment also occurred.
AdaptImmune plans to further development of ADP-A2M4CD8 in ovarian, urothelial, and head and neck cancers. The therapy will be assessed in the phase 2 SURPASS-3 trial in ovarian cancer starting in late 2022 or early 2023 as a monotherapy or combination therapy with nivolumab. The company will continue to enroll patients with urothelial and head and neck cancers in the ongoing SURPASS trial. The therapy is also being evaluated in gastroesophageal cancers in the phase 2 SURPASS-2 trial (NCT04752358) which initiated in 2021 and AdaptImmune plans to assess the therapy in combination with a PD-1 inhibitor as well as in an earlier line of treatment in this indication.
“Emerging data signals encouraging clinical outcomes, especially for gastroesophageal and ovarian cancers for which 2 phase 2 trials have been or will be initiated,” Hong concluded his presentation.1
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