Profound Radiographic and Tumor-Lytic Response of Locally Advanced Pancreatic Adenocarcinoma to a Non-Systemic-Chemotherapy Multimodal Protocol—Fractionated Radiotherapy with Capecitabine Radiosensitization, Intratumoral EpCAM/CD3 Bispecific Antibody, Allogeneic NK and Autologous Lymphocyte Cellular Therapy, and Sequenced Pembrolizumab Following Failure of Conventional Gemcitabine-Based Therapy

Introduction: Locally advanced pancreatic adenocarcinoma (LAPC) carries a dismal prognosis with conventional therapy. Patients who progress on or plateau after first-line gemcitabine-based chemotherapy have limited evidence-based options outside of further cytotoxic regimens or palliative care. We report a case of profound radiographic and tumor-lytic response of bulky LAPC to a multimodal non-systemic chemotherapy protocol delivered after conventional standard of care had been exhausted. Case: A 56-year-old man originally diagnosed with pancreatic adenocarcinoma involving the bile duct in March 2023 received three cycles of gemcitabine at Mayo Clinic (Rochester, MN). His August 2024 PET/CT documented a partial response (pancreatic head SUV-max 3.0, down from 4.1). Over the subsequent 17 months, however, the disease progressed locoregionally. At admission to ICCA CancerCare (Hesieg Hospital, Tijuana, Mexico) on 26 January 2026, contrast CT documented a bulky pancreatic mass involving the bile duct measuring 101.3 mm × 93.68 mm. Intervention: The patient was treated 26 January–6 February 2026 with a multimodal protocol comprising (i) fractionated radiotherapy, 35 Gy in 10 sessions to the pancreatic tumor and adjacent lymph nodes; (ii) oral capecitabine 500 mg daily for 30 days as radiosensitization; (iii) two image-guided intratumoral injections of an EpCAM/CD3 bispecific T-cell-engaging antibody under ultrasound guidance and local anesthesia; (iv) four intravenous infusions of allogeneic natural-killer (NK) cells (100 million cells per infusion); (v) two intravenous infusions of autologous lymphocytes; (vi) two intravenous infusions of allogeneic mesenchymal stromal cells (MSCs, 50 million cells per infusion); (vii) two intravenous infusions of high-dose vitamin C; (viii) IV multivitamin/electrolyte support; (ix) IV esomeprazole 40 mg; and (x) anemia management with intravenous ferric carboxymaltose 500 mg twice and subcutaneous erythropoietin 2000 IU four times. The patient received no systemic cytotoxic chemotherapy at any point during ICCA care; capecitabine was administered at a sub-cytotoxic dose for radiosensitization only. Pembrolizumab (100 mg/4 mL) was administered on 18 March 2026, sequenced approximately six weeks after completion of the loading-phase EpCAM injections. A third intratumoral EpCAM injection was delivered on 15 April 2026. Outcome: Between completion of radiotherapy and administration of pembrolizumab, the tumor underwent clinically evident lysis, liquefying and draining through the patient’s biliary catheter—a phenomenon consistent with the tumor-lytic effect of EpCAM/CD3 bispecific T-cell engagement that radiotherapy alone does not produce. Follow-up contrast CT on 13 May 2026 demonstrated a reduction in tumor dimensions to 87 mm × 72.9 mm with extensive necrotic areas within the residual mass—a substantial volumetric reduction with radiographic evidence of internal necrosis. Surveillance ¹⁸F-FDG PET/CT (14 May 2026) demonstrated only mild residual hypermetabolic activity in the pancreatic head, no bulky or hypermetabolic adenopathy, and no findings concerning metastasis. Conclusions: This case demonstrates that profound radiographic response, including clinically evident tumor lysis, can be achieved in bulky LAPC after failure of conventional gemcitabine chemotherapy using a multimodal protocol combining fractionated radiotherapy with capecitabine radiosensitization, intratumoral EpCAM/CD3 bispecific T-cell-engaging antibody, allogeneic NK and autologous lymphocyte cellular therapy, allogeneic MSC support, and sequenced pembrolizumab—without systemic cytotoxic chemotherapy and without surgical resection. The mechanistic framework (cancer-stem-cell-targeted T-cell engagement with cold-to-hot tumor microenvironment remodeling and cellular immune reinforcement) and the observed tumor-lytic clinical course warrant prospective evaluation in a registry cohort.