Phase II Trial of Vemurafenib and Sorafenib Combination in Advanced KRAS-Mutated Metastatic Pancreatic Cancer.

MAPK activation through KRas, NRas or BRaf mutation occurs in approximately 70% of colorectal cancer patients. Due to their epithelial origin, colorectal tumors generally have high levels of EGFR expression and activation. EGFR therapies such as cetuximab are effective for treatment of a subset of colorectal cancer, particularly patients with wild type (WT) KRas. EGFR signaling is also recently identified as a key resistance mechanism in BRaf mutant colorectal cancer to BRaf inhibitors. In this study, we have genetically characterized 78 patient-derived xenograft (PDX) models of colorectal tumors, and conducted an “n = 1” (single mouse per treatment group) trial in these PDX models with cetuximab, LSN3074753, a pan-Raf and Raf dimer inhibitor, and their combination in collaboration with Oncotest GmbH and Champions Oncology. Among these 78 PDX models, 42 (53.8%) have a KRas mutation, 12 (15.4%) have BRaf V600E or an atypical BRaf mutation, and 26 (33.3%) are WT KRas and BRaf. Consistent with clinical results, cetuximab is primarily active in WT KRas and BRaf PDX models, with disease control rate (DCR) of 53.8% (14/26) in this subgroup. These results suggest that the mouse n = 1 PDX trial paradigm could reliably predict clinical results. For pan-Raf and Raf dimer inhibitor LSN3074753, it is active in a subset of PDX models, particularly those with BRaf or KRas mutation(s), with DCR of 21.2% among models with a KRas or BRaf mutation. Importantly, a synergistic effect is observed when cetuximab and LSN3074753 are combined for treatment of these 78 PDX models. The overall DCR in the combination arm is 50% (39/78), while cetuximab or LSN3074753 alone has an overall DCR of 24 or 18%, respectively. Further statistical analyses reveal that BRaf mutations including V600E or other atypical mutations (G469E, G76E, G596V, G203V, etc) are the best predictor of combination synergy, and are significantly associated with synergistic effect with a p value of 0.004. In models with BRaf mutations, the combination arm has a DCR of 50% (6/12), whereas cetuximab or LSN3074753 alone has a DCR of 8.3 or 17%, respectively. BRaf or KRas mutations are also significantly associated with combination synergy with p value of 0.01. Among 42 KRas mutation models, LSN3074753 or cetuximab alone has a DCR of 21.4 or 16.7%, and the combination arm has a DCR of 43%. Overall, these results indicate that combination of EGFR and Raf inhibition by cetuximab and a pan-Raf inhibitor has the potential for treatment of colorectal cancer patients with BRaf or KRas mutation. Citation Format: Yung-mae M. Yao, Gregory P. Donoho, Philip W. Iversen, Yue Wang Webster, Yong Gang Yue, James R. Henry, Gregory D. Plowman, Sheng-Bin Peng. Mouse PDX Trial Suggests Combination Efficacy of Raf and EGFR Inhibition in Colorectal Cancer with BRaf or KRas mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-004. doi:10.1158/1538-7445.AM2015-LB-004

e15781 Background: Pancreatic cancer remains a leading cause of cancer death with limited treatment options. After promising results from a retrospective chart review of the combination of irinotecan, oxaliplatin, and cetuximab (OIC), a prospective phase II trial was conducted to determine the efficacy and safety of this novel combination regimen in patients with advanced pancreatic cancer. Methods: Patients aged 18 and older, with a performance status of 0-2, and a life expectancy of minimum 12 weeks were eligible if they had confirmed locally advanced or metastatic pancreatic cancer. Patients were treated with intravenous irinotecan at 90 mg/m2, oxaliplatin at 60 mg/m2, and cetuximab at 250 mg/m2on day 1 of a 14-day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary efficacy endpoint was objective response rate (ORR) and disease control rate (DCR) per RECIST 1.1 criteria. The secondary endpoints included progression free survival (PFS), overall survival (OS), and tolerability of the regimen. Results: 60 patients were enrolled and 58 were evaluable; of these, 78% had metastatic disease and 22% had locally advanced cancer at time of enrollment. 41.4% of patients had received at least one prior line of cytotoxic chemotherapy. The ORR and DCR were 6.9% and 58.6%, respectively (complete response n = 1; partial response, n = 3; stable disease, n = 30). The median PFS was 3.6 months [95 % confidence interval (CI): 2.24-4.31], and median OS was 4.8 months [95 % CI: 3.68-6.25]. The most common grade 3 or 4 toxicities were hypokalemia (20.7%), fatigue (17.2%), abdominal pain (15.5%), hyperglycemia (13.8%) and dehydration (13.8%). Conclusions: OIC on a two-week regimen was well tolerated and demonstrated a high disease control rate, encouraging further investigation of this regimen in advanced pancreatic cancer. Clinical trial information: NCT00871169.

e16365 Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor with an immunosuppressive microenvironment. Immune checkpoint inhibitors (ICIs), either alone or with chemotherapy, have shown disappointing results in advanced pancreatic cancer. Chidamide, a subtype-selective histone deacetylase inhibitor, enhances chemotherapy, immunotherapy, and endocrine therapy. Approved for peripheral T-cell lymphoma, diffuse large B-cell lymphoma, and hormone receptor-positive advanced breast cancer, chidamide also demonstrates efficacy in other tumor types. This ongoing study evaluates the efficacy and safety of combining adebrelimab with chidamide, gemcitabine, and S-1 as first-line therapy for locally advanced or metastatic pancreatic cancer. Methods: This prospective, single-arm, multicenter phase II trial included patients aged 18–75 with histologically confirmed locally advanced or metastatic pancreatic cancer, naïve to any therapy except biliary stenting, and with at least one measurable lesion. Patients received adebrelimab (1200 mg IV, D8), chidamide (20 mg PO, BIW, D8, 11, 15, 18), gemcitabine (800–1000 mg/m 2 IV, D1, 8), and S-1 (40–50 mg PO, BID, D1–14) on a three-week cycle. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. Results: As of December 27, 2024, 13 patients were enrolled. The ORR was 62% (8/13), with a DCR of 92% (12/13). The median time to response was 1.66 months, with median PFS and OS of 9.0 and 14.2 months, respectively. CA199 levels decreased in patients with a tumor response; all with ≥40% reduction in CA199 had an objective response. Common treatment-related adverse events (AEs) included anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, increased D-dimer, aspartate transferase levels, and lymphopenia. Grade ≥3 AEs occurred in 23% (3/13) of patients, including leukopenia (23%) and thrombocytopenia (15%). All AEs resolved with symptomatic treatment, and no patients withdrew due to AEs. Conclusions: Chidamide enhanced the efficacy of immunotherapy and chemotherapy, improving outcomes compared to chemotherapy alone or in combination with immunotherapy. The ADEPT regimen showed promising antitumor activity and favorable tolerability as first-line therapy for locally advanced or metastatic pancreatic cancer. Further data from a large cohort and longer follow-up will be presented. Clinical trial information: NCT06584227 . Efficacy data. PFS (m) OS (m) ORR (%) DCR (%) TTR (m) Median 9.0 14.2 62 92 1.66 95% CI 7.0–13.3 5.2–NE 31.58–86.14 63.97–99.81 1.43–1.99 CI, confidence interval; DCR, disease control rate; m, month; NE, not estimable; OS, overall survival; ORR, objective response rate; PFS, progression-free survival; TTR, time to response.

Objective: To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues. Methods: From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed. Results: This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage (HR=1.47, 95% CI: 1.06-2.04), primary tumor site (HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score (HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy (HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site (HR=0.68, 95% CI: 0.48-0.95), ECOG score (HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy (HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death (P＜0.05). Conclusion: Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Introduction: K-Ras mutant cancers such as pancreatic cancer are a major cause of cancer-related death and are difficult to treat, with a five-year survival rate of less than 6%. It is reported that oncogenic K-Ras signaling passes through RAF/MEK/ERK pathways. Selumetinib (AZD6244) is a selective MEK inhibitor for K-Ras mutant cancers dependent on mitogen-activated protein kinase (MAPK) signaling pathway and is currently in phase II trials. However, the underlying mechanisms of action are not well known. Autophagy is a self-digest pathway to degrade cellular organelles and macromolecules in maintaining proteome homeostasis, and it is suppressed by the mammalian target of rapamycin complex 1 (mTORC1), a master regulator of translation and autophagy. mTOR activity is known to be activated by AMP-activated protein kinase (AMPK) and negatively regulated by c-Jun N-terminal kinase 1/2 (JNK1/2) MAPK signaling. Autophagy is thought to play protective and suppressive roles in cancer; however, the molecular basis for the relationship between the induction of autophagy and the initiation of pancreatic malignancy is currently unknown. Heat shock factor 1 (HSF1), a key transcription factor involved in proteotoxic stress response via protein-folding. HSF1 plays a pro-oncogenic role in the development of cancer by regulating signaling transduction and translation during tumorigenesis. HSF1 is reportedly hyperactive in pancreatic cancers. AZD6244 reportedly decreases HSF1 phosphorylation at Ser326 and HSF1 expression in melanomas and therefore abates cancer development. However, the detailed mechanism by which HSF1 engages in AZD6244-mediated autophagy in K-Ras mutant human pancreatic cancer is not fully understood. Objectives: This study aims to investigate the role of HSF1 in AZD6244-mediated autophagy in K-Ras mutant human pancreatic cancer. Methods and Results: AZD6244 induces robust autophagy response in human pancreatic cells with hyperactive K-Ras signaling. Simultaneously, AZD6244 reduces HSF1 phosphorylation at Ser326 and HSF1 expression in human pancreatic cancer cells. Intriguingly, genetic deletion of HSF1 induces autophagy under starvation condition. In addition, AZD6244 induces phosphorylation of AMPK Ser172 and JNK1/2 T183/Y185 and decreases mTORC1 activity in human pancreatic cancer cells. Pharmaceutical inhibition of AMPK or genetic deletion of JNK1/2 prevents AZD6244-induced autophagy. Furthermore, HSF1 knockdown induces phosphorylation of Unc-51-like kinase 1(ULK1) Ser555 and decreases ULK Ser757, which is mediated by AMPK and mTOR, respectively. Conclusion: HSF1 plays an integral role in Selumetinib-mediated autophagy through AMPK and/or JNK1/2 signaling in K-Ras mutant human pancreatic cancer cells. Citation Format: Shruti Ghai, Alex Young, Kuo-Hui Su. Novel effect of Selumetinib-mediated autophagy via HSF1 in K-Ras mutant pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3004.

Locally Advanced Non-Metastatic Pancreatic Cancer — Can We Do More?

BackgroundPancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence.MethodsPubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively.ResultsA total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%), disease control rate was 55.0% (95% CI: 51.5%–58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease.ConclusionOur study showed that GemErlo is associated with reasonable activity in treating patients with locally advanced or metastatic pancreatic cancer. Most of the AEs were tolerable, while some severe AEs needed careful detection.

O3-005 - Phase 1 and 2 Trials of Combination Therapy with Gemcitabine and Candesartan in Advanced Pancreatic Cancer

Objective To value the clinical efficacy and toxicity of S-1 compared to gemcitabine combined with S-1 in treatment of patients with advanced pancreatic cancer. Methods From January 2011 to December 2013, the data of 46 patients with advanced pancreatic cancer were analyzed retrospectively, including 24 patients receiving S-1 alone (group A) and 22 patients who received gemcitabine combined with S-1 (group B). The results were evaluated by objective response rate (ORR), disease control rate (DCR), survival time and safety. Results In group A the ORR was 20.8 % (5/24), DCR was 66.7 % (16/24), median progression-free survival was 4.8 months, median overall survival was 9.6 months, and 1 year survival was 12.5 %. In group B the ORR was 27.3 % (6/22), DCR was 72.7 % (16/22), median progression-free survival was 5.9 months, median overall survival was 10.3 months, and 1 year survival was 22.7 %. There was no significant difference between the two groups (P>0.05). The incidence rates of leukopenia, neutropenia and thrombopenia in group A were significantly lower than those in group B (P<0.05). Conclusion S-1 alone and gemcitabine combined with S-1 have similar effects in the treatment of advanced pancreatic cancer, but the toxicity of S-1 is mild and tolerable. Key words: Pancreatic neoplasms; S-1; Gemcitabine

Introduction:To report response rates, progression-free survival (PFS) and overall survival (OS) in patients with advanced pancreatic cancer treated with different available chemotherapeutic regimens over 10 years.Materials and Methods:This is a retrospective observational study. All patients with locally advanced and metastatic pancreatic cancer (MPC) at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from January 2008 to December 2017 were studied. Data were collected from the hospital information system. The characteristics and outcomes of all the patients were analysed. PFS and OS were also estimated. Kaplan–Meier curves and log-rank test were applied, and SPSS version 20 was used for data analysis.Results:Eighty-seven subjects with a median age of 56 years (range 21–76) were included. Sixty-two (71%) subjects were male. The most common tumour location was the head of the pancreas in 46 (53%) of all the subjects. Sixty-three (72%) subjects had elevated carbohydrate antigen-19.9 values. About 47 (54%) subjects had locally advanced pancreatic cancer (LAPC), and 40 (46%) subjects had MPC. Chemotherapy regimens used were FOLFIRINOX in 23 (26%), gemcitabine (GEM) based in 66 (65%) and capecitabine (CAP) based in 8 (9%) of the subjects. One (1%) subject had a complete response, 12 (14%) had a partial response, 10 (11%) had stable disease and 59 (68%) of the subjects had progressive disease. The objective response rate (ORR) was 15% and the disease control rate (DCR) was 26%. In MPC, the ORR was 10%, DCR was 18% and tumour progression was seen in 72% of the patients, while in LAPC, the ORR was 19.1, DCR 34% and tumour progression was documented in 64% of the patients, respectively. The FOLFIRINOX chemotherapy regimen had better ORR, DCR and lesser number of progressions as compared to GEM- and CAP-based chemotherapy regimens. The median PFS of the whole group was 32 weeks, and the median OS was 54 weeks. The PFS was significantly higher for LAPC (39 weeks) as compared to the MPC group (25 weeks) (P = 0.028). There was no statistically significant difference between the OS of these two groups (P = 0.451). In addition, PFS was significantly higher with FOLFIRINOX chemotherapy as compared to the other chemotherapy regimens. Regarding OS, there was no statistically significant difference among all chemotherapy regimen groups (P = 0.267).Conclusion:Based on our results, FOLFIRINOX remained the most effective chemotherapy regimen despite the dose modifications and toxicities in all groups, indicating that modified FOLFIRINOX could be considered as a first-line regimen in Southeast Asian population.

Targeting KRAS Mutations

Objective To establish a method of detection kirsten rat sarcoma viral oncogene mutations in plasma by a nano capture probe system, and to explore the relationship between clinical pathology stage, or prognostic and K-ras single nucleotide polymorphism mutations in patients with pancreatic cancer. Methods The plasma samples of 72 patients with pancreatic cancer were collected from June 2013 to September 2015. The diagnosis of all patients were explicit. The DNA were extracted from all plasma samples and were detected for the codon 12 and 13 mutation of K-ras gene by nano capture probe. The relationship between clinical pathology factors, or prognostic and K-ras point mutations in pancreatic cancer was analyzed via clinical data. Results The plasma DNA concentration of 72 patients with pancreatic cancer was 20-200 ng/μl, 33 patients were detected for K-ras gene mutation, the cycle threshold (Ct) value was 21.71-35.61, including 30 patients for codon 12 mutation and 3 patients for codon 13 mutation, the K-ras mutation rate was 45.8% (33/72). 10 of 37 patients with early pancreatic cancer (stage Ⅰ and Ⅱ) were detected for K-ras gene mutation, the mutation rate was 27.0% (10/37), but 23 of 35 patients with advanced pancreatic cancer (stage Ⅲ and Ⅳ) were detected for K-ras gene mutation, the mutation rate was 65.7% (23/35), the difference is statistically significant (χ2=10.843, P=0.001), it is suggested that K-ras mutation in plasma is ralated to tumor stage. All 72 patients with pancreatic cancer were followed up, the follow-up time was 2 months to 26 months, the average follow-up time was 9.7 months. The one-year survival rate of patients with K-ras mutation is 42.6%, and the one-year survival rate of patients with wild genotype is 73.4%, the difference is statistically significant (χ2=5.335, P=0.017)). Conclusion The nano capture probe system could certainly detect K-ras mutation in rare plasma DNA. K-ras mutation in plasma is related to TMN stage and prognosis of pancreatic cancer, and K-ras mutation in plasma DNA is a predictive biomarker for a poor prognosis of pancreatic cancer patients. Key words: Pancreatic cancer; Prognosis; Mutation; Magnetic nanoparticles

Evaluating the Impact of Combination of Nivolumab and Ipilimumab to Liver/Lung SBRT on Local Control for Colorectal and Pancreatic Cancer: A Pooled Analysis of Two Prospective Trials

Introduction: Nanoliposomal irinotecan (nal-IRI) + 5-fluorouracil (FU)/leucovorin (LV) is the new standard second-line therapy for advanced pancreatic cancer (PC). Tegafur, gimeracil, and oteracil potassium (S-1) have been used in advanced PC after gemcitabine (GEM) plus nab-paclitaxel treatment, but the clinical difference between nal-IRI+5-FU/LV and S-1 remains unclear. Methods: We retrospectively compared the efficacy and safety of nal-IRI+5-FU/LV and S-1 in patients with advanced PC refractory to GEM plus nab-paclitaxel. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: We analyzed patients with advanced PC who were refractory to GEM plus nab-paclitaxel from May 2015 to January 2022 at our hospital. Twelve patients treated with nal-IRI+5-FU/LV and 51 patients treated with S-1 were included in this study. Comparing the nal-IRI+5-FU/LV and S-1 groups, the median PFS was 2.95 months versus 2.10 months (p = 0.658), respectively, and the median OS was 8.51 months versus 5.83 months (p = 0.763), respectively. The ORR and DCR were 8.3% and 2.0% (p = 0.347) and 58.3% and 49.0% (p = 0.750) for the nal-IRI+5-FU/LV and S-1 groups, respectively. There were no significant differences in adverse events between the two groups. In a subgroup analysis, patients under 65 years of age treated with S-1 had a significantly better median OS (HR, 3.46; 95% CI: 1.02–11.71, p = 0.046). Conclusion: Nal-IRI+5-FU/LV and S-1 were equally effective and safe as second-line therapy for PC. However, the results suggest that S1 is an option for younger patients, especially those under 65 years.

e15756 Background: Pancreatic cancer (PC) is one of the most aggressive and death-relating malignancy. Gemcitabine (GEM) is the key agent in the first-line standard regimen for advanced PC, which is mostly diagnosed at advanced stage and unsuitable for curative resection. The objective responsive rate (ORR) and medium progression free survival (PFS) of various GEM-based regimens are still unsatisfied. Therefore, development of new therapeutic modalities, including immunotherapy, is needed. This study is to investigate the efficacy, safety and clinical beneficial of combination neoantigen based immunotherapy with GEM and radiotherapy in locally advanced and metastatic PC patients. Methods: Three locally advanced unresectable and seven metastatic PC patients received at least two cycles of GEM (1000mg/m2 on day 1 and day 6), radiotherapy combing with neoantigen induced DC vaccination on day 7 and cytotoxic T lymphocyte transfer from day 12 to 15 (repeated every 21 days). The locally advanced unresectable PC patients received stereotactic body radiotherapy (SBRT) with a total amount of 50-66Gy during the first cycle. For metastatic patients, their partial lesions received a low dose radiation (0.5Gy bid*2days ) on day 10 and 11 in each cycle. Results: Two cases were observed with partial remission (PR), five with stable disease (sd), and three with progressive disease (PD). The disease control rate (DCR) was 70%. Median progression free survival (PFS) was 6.4 months. After the first treatment cycle, the total effectiveness for pain easement and increasing appetite are 100% (8/8)and 66.7%, respectively. Haematotoxicities with a 40% incidence rate were the most common adverse drug reactions. Two patients had grade 1 to 2 neutropenia, two with grade 3 to 4 thrombocytopenia. Three patients suffered grade 1 to 2 gemcitabine-induced skin rash. No treatment-related mortality occurred. Conclusions: Neoantigen reactive T cells combined chemoradiotherapy demonstrated an acceptable response and safety in advanced pancreatic cancer patients.