Personalized peptide vaccine induced adoptive immunocyte transfer combined chemotherapy and radiation improved the survival of advanced pancreatic cancer

14047 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 and report the results of the phase I trial. Methods: The subjects had unresectable pancreatic ductal cancer. The method of administration was single administration of GEM on the first day of the week from Level 1 to Level 4 at 400 to 1000 mg/m2, with concurrent administration of S-1 at 40 to 100 mg/day × 7 days, repeated every other week as a collaborative trial conducted at 3 facilities. The purpose was to determine the optimal dose with adverse events as an indicator. Results: Eighteen patients were enrolled (3 each at Levels 1, 2, 3 and 4’, 6 at Level 4). Average age was 60.9 years (38 - 71 years). There was no dose limiting toxicity (DLT) up to Level 3. Level 4 was the maximum tolerated dose since DLT was observed in 4/6 patients (mucositis 2, rash 1, anorexia 1), and no DLT was observed in 3 additional patients at Level 4’. The resulting recommended dose was Level 4 (GEM 1000 mg/m2, S-1 100 mg/day). For reference, partial response was observed in 5 patients, and median survival time at this stage is 336±39 days. Conclusions: The recommended dosage of GEM + S-1 combined chemotherapy for unresectable advanced pancreatic cancer was determined in a phase I trial. We intend to proceed to a phase II trial. No significant financial relationships to disclose.

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A phase II multicentric trial of combined chemotherapy with gemcitabine plus S-1 in patients with advanced pancreatic cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15129 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15129-15129

Author(s):

S. Ohkawa ◽

A. Amano ◽

M. Ueno ◽

K. Miyakawa ◽

K. Sugimori ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase I ◽

Survival Time ◽

Median Survival ◽

Phase Ii ◽

Median Survival Time ◽

Progressive Disease ◽

Advanced Pancreatic Cancer ◽

Combined Chemotherapy ◽

Standard Drug

15129 Background: While gemcitabine (GEM) is the standard drug for chemotherapy against advanced pancreatic cancer, the development of multidrug therapies for improved outcome is important. We conducted multicentric combined chemotherapy with GEM and S-1 trial and reported the results of the phase I trial last year. And this phase II study evaluated the efficacy and feasibility. Methods: The subjects had unresectable pancreatic ductal cancer. Eligibility criteria were pathologically-proven, Karnofsky performance status 80 to 100%, age 20 to 74 years, adequate hematological, renal, and liver functions and written informed consent. The method of administration was single administration of GEM on the first day of the week 1000 mg/m2, with concurrent administration of S-1 at 80 (<1.5 m2) to 100 (=1.5 m2) mg/day × 7 days, repeated every other week until the progressive disease or life threatening adverse events. This administration dose was determined from the result of the phase I study. The primary endpoint was median survival time. And the secondary endpoints were the overall response rate and the toxicities. Results: 40 patients(pts) were enrolled. Average age was 62.9±8.3 years (34–73 years). Thirty nine pts were conducted this therapy except one who refused this study before the start of administration. Thirty eight pts were evaluable for response, partial response, stable disease, progressive disease were observed in 7 (17.5%), 21 (52.5%) and 10 pts (25.0%), respectively. The median survival time at this stage is 276±51 days in this ongoing study. Grade 3 and 4 toxicities were mainly leucocytes(10 pts), neutrophils(8 pts) and anorexia(6 pts). Conclusions: The GEM plus S-1 combined chemotherapy is effective and feasible in patients with advanced pancreatic cancer. No significant financial relationships to disclose.

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The development of therapeutic cancer vaccine for pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.707 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 707-707

Author(s):

Hiroki Yamaue ◽

Motoki Miyazawa ◽

Masahiro Katsuda ◽

Manabu Kawai ◽

Seiko Hirono ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Cancer Vaccine ◽

Phase Ii Study ◽

Peptide Vaccine ◽

Advanced Pancreatic Cancer ◽

Pancreatic Ductal Carcinoma ◽

Adjuvant Setting ◽

Multicenter Phase ◽

Ctl Responses

707 Background: A previous phase II/III trial using a single cancer peptide vaccine derived from vascular endothelial growth factor receptor (VEGFR)2 for patients with advanced pancreatic cancer did not demonstrate the overall survival (OS) benefit (Yamaue et al. Cancer Sci 2015). However, for the next trial, we conducted a multicenter phase II study using multipeptide cocktail vaccine named OCV-C01 derived from a novel higher immunogenic antigen KIF20A, VEGFR1 and VEGFR2 combined with gemcitabine in postoperative adjuvant setting. Methods: A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks, and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8, and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, OS and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. Results: The median DFS was 15.8 months (95% confidence interval (CI), 11.1-20.6), and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with and without KIF20A-specific CTL responses (p = 0.027), and between patients with and without KIF20A expression in resected pancreatic cancer tissues (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. Conclusions: OCV-C01 combined with gemcitabine was tolerable with a favorable median DFS of 15.8 months. In cancer vaccine treatment, positive expression of targeted antigen was essential, and postoperative adjuvant setting was more suitable than advanced state of cancer. Clinical trial information: UMIN000007991.

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