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4622 Background: Immunotherapy is emerging as a potent therapy for a range of hematologic malignancies and solid tumors. To target pancreatic carcinoma we have developed an autologous, non-engineered T cell therapy using T cell lines that simultaneously target the tumor-associated antigens (TAAs) PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin. These multiTAA-specific T-cell lines could be consistently prepared by culturing PBMCs in the presence of a Th1-polarizing/pro-proliferative cytokine cocktail, and adding autologous pepmix-loaded DCs as APCs. Methods: Patients with locally advanced or metastatic pancreatic adenocarcinoma who achieved cancer control with three months of standard chemotherapy were eligible to receive up to 6 infusions of multiTAA T-cells (fixed dose - 1x107 cells/m2). While also continuing the same chemotherapy, T-cells were given at monthly intervals from month four, onwards. The primary study endpoints were safety and feasibility of completing all 6 planned infusions, with secondary and tertiary endpoints including anti-tumor effects, patient survival, in vivo expansion and T cell persistence of the infused cells as well as recruitment of the endogenous immune system. Results: Between June 2018 and December 2019, we treated 13 patients with multiTAA T-cells. For 12/13 patients, we generated sufficient cells for all 6 planned doses; 2 doses were available for the remaining patient. Of the 13 patients, 8 maintained cancer control for a longer than expected duration, compared to historical controls. With administration of T-cells, 3 of these 8 patients had partial responses and 1 patient had a radiographic complete response (per RECIST). These responses were seen in patients with metastatic cancer. Notably, no patient had infusion-related systemic- or neuro-toxicity. Thus, infusion of autologous multiTAA-targeted T cells directed to PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin has been safe and provided durable clinical benefit to patients with pancreatic adenocarcinoma. Conclusions: Autologous, TAA cytotoxic T-cells can reliably be generated and safely administered to patients in conjunction with standard of care chemotherapy. In some patients, addition of T-cells may extend duration of first line therapy cancer control and induce additional tumor responses, and activation of the endogenous immune system has been documented in all patients. Exploration in a higher phase study is warranted. Clinical trial information: NCT03192462 .

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A 57-year-old white woman presented to an outside hospital with shortness of breath. She was noted to have bilateral pleural effusions and an intra-abdominal cystic mass on a computed tomography (CT) scan. Diagnostic thoracentesis was performed at that time. The cytology showed adenocarcinoma cells, which were consistent with metastatic spread from ovarian primary. Debulking surgery was performed at the outside hospital that consisted of a total abdominal hysterectomy with bilateral salpingooophoerectomy, appendectomy, cholecystectomy, and partial colectomy of the transverse colon. Pathology was consistent with grade 2 to 3 papillary cystadenocarcinoma.Repeat CT 1 month after surgery revealed small bilateral pleural effusions and bilateral axillary lymphadenopathy. The initial postsurgical, prechemotherapy cancer antigen (CA) -125 of the patient was 1,160 U/mL (normal value, Ͻ 35 U/mL). The patient was started on carboplatin and paclitaxel doublet chemotherapy 1 month after surgery at our facility. Her CA-125 after completion of chemotherapy had decreased to 18 U/mL. One year later, the CA-125 level of the patient increased to 40.3 U/mL, and a restaging CT scan revealed no evidence of local tumor recurrence but did indicate a superior mediastinal lymph node, which had increased in size since the previous year. A positron emission tomography scan was performed that did not confirm disease recurrence. The patient was observed for the next 3 years.The family history of the patient was significant for breast cancer in two sisters and in two nieces from the same sisters, all of whom were positive for BRCA2 mutation. A third sister had a history of lung cancer and colon cancer. The mother of the patient had a history of breast cancer and lung cancer, and both the father and brother of the patient had melanoma. The patient was positive for deleterious mutation BRCA2-(4075delGT) and BRCA2 polymorphism (L996R).The patient presented for follow-up in May 2011 with complaints of a 1-month history of mild headaches and jerking movements in her right arm as well as occasional dizziness and decreased visual acuity. Magnetic resonance imaging of her brain revealed a solitary mass in the left central parietal region (Fig 1). She was admitted to the hospital and started on intravenous steroids and underwent craniotomy with removal of the tumor. The pathology of the specimen revealed a metastatic poorly differentiated adenocarcinoma, with patchy positive immunohistochemical staining for progestrone receptor and estrogen receptor, which was compatible with metastasis from ovarian primary (Fig 2). Repeat CT imaging of her chest, abdomen, and pelvis did not reveal recurrence of disease in any other locations. Her CA-125 had remained relatively stable over the past 3 years and was 38.1 U/mL at the time of brain surgery. The patient was discharged with mild improvement of her symptoms and scheduled for wholebrain radiation therapy as well as platinum-based chemotherapy.The patient completed 10 fractions of whole-brain radiation therapy....

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.