Multiantigen-Targeted T Cells Safe/Feasible in Locally Advanced PDAC

An autologous multiantigen-targeted T cell therapy yielded clinical outcomes associated with treatment-emergent antigen spreading, as well as peripheral expansion of tumor-associated antigens-targeted T cell clones, in patients with pancreatic ductal adenocarcinoma (PDAC). Results were found in the first-in-human phase 1/2 TACTOPS trial (NCT03192462), which was published in Nature Medicine.¹

Patients were split into 3 separate trial arms: arm A, patients had stage III or IV disease that was stable or responding to at least 3 months of chemotherapy; arm B, patients had stage III or IV disease that had not progressed after chemotherapy; and arm C, patients had potentially resectable disease and received their initial T cell infusion between neoadjuvant therapy and planned surgery.

Across the 37 treated patients, a total of 140 infusions were received. Adverse events attributed as possibly being related to multi-antigen T cell infusions were noted in 64.9% of patients. One of those events was grade 3 lipase elevation classified as a treatment-related serious AE and thus was the only serious event; the event occurred 3 days after the fifth T cell infusion, and the patient was discharged within 24 hours with no further symptoms. No instances of cytokine release syndrome (CRS) or neurotoxicity were observed.

“Generating a sufficient number of T cells for 6 cell infusions was feasible, even in heavily pretreated participants and infusions were well tolerated, whether administered alone or with standard PDAC-targeted chemotherapy, because only a single grade 3 treatment-related serious AE [transient lipase elevation] was reported, without any cases of CRS,” wrote lead study author Benjamin L. Musher, MD, a professor of medicine and the medical director of medical oncology at the Dan L Duncan Comprehensive Cancer Center of Baylor College of Medicine, and coauthors, in the paper.

In arm A, the best response rate after 1 infusion was 7.7% complete responses (CR; n = 1), 15.4% partial responses (PR; n = 2), 61.5% stable disease (n = 8), and 15.4% progressive disease (n = 2). The overall response rate (ORR) was 23.1% (95% CI, 5.0%-53.8%), and the disease control rate (DCR) was 84.6% (95% CI, 54.6%-98.1%). It was noted that the 3 patients who responded to treatment had stable disease prior to study entry.

The median duration of response (DOR) was 7.5 months (range, 3.5-16.6) in those who achieved a PR or CR compared with 6.3 months (range, 0.7-16.6) in those with a CR, PR, or stable disease. Additionally, the median event-free survival (EFS) and overall survival (OS) were 6.4 months (95% CI, 2.4-9.5) and 14.1 months (95% CI, 3.6-15.4).

In arm B, no objective responses were recorded, with 25% and 75% having stable disease and progressive disease, respectively. The ORR was 0%, and the DCR was 25.0% (95% CI, 5.5%-57.2%). The median EFS and OS were 2.2 months (95% CI, 1.2-2.5) and 4.4 months (95% CI, 1.5-16.7).

In arm C, 75% of patients proceeded to have planned resection (n = 9) and 25% had unresectable or metastatic disease at the time of surgery (n = 3). Two of the 9 patients who were resected remained alive and disease-free after 66 months of follow-up, despite being relatively high risk.

The median EFS and OS for all patients in arm C were 7.5 months (95% CI, 2.6-39.7) and 12.6 months (95% CI, 4.5-45.9), respectively. For those who were resected, the median relapse-free survival and OS were 11.5 months (95% CI, 3.3-not available [NA]) and 25.3 months (95% CI, 5.4-NA).

Further, across all study arms, patients who received more infusions appeared to do better than those who received fewer infusions. Notably, evidence of progression precluded continuing with infusions, so the analysis was confounded.

“Although efficacy was not the primary end point of this trial, objective clinical responses were observed, albeit primarily in arm A, in which patients were also receiving chemotherapy,” said the authors.

TACTOPS was a nonrandomized, 3-arm, single-center trial run at the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine. Eligible patients had locally advanced or metastatic PDAC, were 18 years or older, had at least 3 months of life expectancy, had measurable disease per RECIST v1.1, and an ECOG performance status of 2 or lower.

All patients received up to 6 infusions of autologous multi-antigen T cells at a fixed dose of 1 × 10⁷ cells m^–2 in an arm-specific schema. Patients in arm A received standard of care treatment, with infusions given during the ‘off week’ of chemotherapy to minimize the impact of chemotherapy on the ‘fitness’ of the infused cells. In arm B, T cells were infused every 4 weeks as monotherapy. In arm C, T cells were infused between 1 week and 4 weeks before resection, then every 4 weeks, beginning 8 weeks or more after surgery to address any minimal residual disease remaining after surgical resection of the primary mass.

The T cell infusions targeted 5 tumor-associated antigens. They were: PRAME rabbit polyclonal antibody, SSX2 mouse monoclonal antibody, MAGEA4 mouse monoclonal antibody, Survivin rabbit monoclonal antibody, and NY-ESO-1 mouse monoclonal antibody. The investigators noted that they were chosen based on their tumor specificity, oncogenicity, immunogenicity, and level of expression.

The primary end point of the trial was the safety and feasibility of completing 6 infusions of multi-antigen T cells. Secondary end points were EFS and OS, as well as antitumor immune activity.

“Combining TAA T cells with other new immunotherapies and/or standard-of-care chemotherapy, or possibly as a single therapeutic modality in a strategic way, warrants further investigation,” concluded the study authors.

References

Musher BL, Vasileiou S, Smaglo BG, et al. Autologous multiantigen-targeted T cell therapy for pancreatic cancer: a phase 1/2 trial. Nat Med. Published online January 2, 2026. doi:10.1038/s41591-025-04043-5