T-cell receptor therapy ‘definitely effective’ for metastatic solid tumors
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More than a third of patients with solid tumors showed evidence of antitumor response after treatment with ADP-A2M4CD8, according to data presented at the virtual ESMO Congress.
The investigational T-cell receptor (TCR) therapy also conferred a disease control rate greater than 80%, according to updated results of the phase 1 SURPASS trial.
ADP-A2M4CD8 (Adaptimmune) is a second-generation autologous, gene-edited specific peptide-enhanced affinity receptor (SPEAR) T-cell therapy. The agent is engineered to express the CD8-alpha co-receptor alongside an engineered TCR that targets MAGE-A4 protein on the surface of cancer cells.
Most patients in this study had metastatic disease and were refractory to standard treatment, according to David S. Hong, MD, deputy chair of the department of investigational cancer therapeutics in the division of cancer medicine at The University of Texas MD Anderson Cancer Center.
Patients with metastatic disease refractory to standard treatment typically move to hospice care within a few months, Hong said. However, some patients in the SURPASS trial exhibited durable responses to therapy, with one response lasting up to 9 months.
It is difficult to draw conclusions about the durability of this treatment until more data are available, Hong said.
“But it definitely looks like patients can benefit from this therapy,” he told Healio.
The SURPASS trial is a first-in-human dose-escalation study designed to evaluate the safety and efficacy of ADP-A2M4CD8 for adults who are HLA-A*02-positive and have advanced solid tumors with high expression of MAGE-A4.
The trial included lower dose (0.8 × 109 to 1.2 × 109 cells) and higher-dose (1.2 × 109 to 6 × 109 cells) cohorts, in addition to a dose-expansion cohort (1.2 × 109 to 10 × 109 cells).
Evaluation of the safety and tolerability of ADP-A2M4CD8 served as the study’s primary objective. Assessment of antitumor activity served as a secondary objective.
The study enrolled 25 patients (median age, 58 years; range, 31-75; 52% male) with advanced metastatic disease. The study included patients with synovial sarcoma, myxoid/round cell liposarcoma, melanoma, and ovarian, head and neck, esophageal, bladder or lung cancers.
Eighteen patients (72%) developed cytokine release syndrome (CRS), with four patients (16%) experiencing grade 3 CRS. Eight patients (32%) of patients developed neutropenia; all cases were grade 3 or greater.
Treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in four patients (16%), including two patients (8%) with grade 3 ICANS.
Twenty-two patients were evaluable for response at data cutoff on Aug. 2.
Researchers reported a 36% overall response rate (n = 8), with one complete response (4.5%) — a woman with ovarian cancer — and seven partial responses (32%). Results showed an 86% overall disease control rate.
The results show ADP-A2M4CD8 to be active among more than one-third of patients, and the therapy is “probably safer than what is currently approved,” Hong said.
“We don't have any cures for metastatic cancer — not even the use of checkpoint inhibitors can provide a cure for metastatic disease,” Hong told Healio. “This therapy is not a cure, but it is definitely effective, at least in 36% of patients.”
The first generation of SPEAR T-cell therapy, known as afamitresgene autoleucel, is being evaluated in the SPEARHEAD-1 trial. It has shown promising efficacy and disease control among patients with synovial sarcoma. Hong anticipates this therapy eventually will be approved for commercial use.
His group also plans a phase 2 trial to evaluate the efficacy of next-generation ADP-A2M4CD8 SPEAR T-cell therapy for other solid tumor types.
The next steps to provide a clinically impactful therapy include developing novel ways to target more cancer types and combining it with off-the-shelf cellular therapy derived from healthy donor cells, Hong said.
“This is part of the first steps of seeing cellular therapy have an impact on solid tumors,” Hong said. “The hope is that this therapy will move from being provided only at large medical centers like ours to community centers.”
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Hong DS, et al. Abstract 540P. Presented at: European Society for Medical Oncology Congress 2021 (virtual); Sept. 16-21, 2021.
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