Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac) : an open-label, randomised, phase 3 trial 안녕하십니까 금일 발표할 저널은 telomerase peptide vaccine인 GV1001을 advanced pancreatic cancer에서 gemcitabine과 capcitabine 병합요법에 추가하는 것에 대한 open-label randomised 3상연구에 관한 논문으로 lancet oncology에 2014년에 실린 논문입니다 Gary Middleton, Paul Silcocks, Trevor Cox, Juan Valle, Jonathan Wadsley, David Propper, Fareeda Coxon, Paul Ross, Srinivasan Madhusudan, Tom Roques, David Cunningham, Stephen Falk, Nick Wadd, Mark Harrison, Pippa Corrie, Tim Iveson, Angus Robinson, Karen McAdam, Martin Eatock, Jeff Evans, Caroline Archer, Tamas Hickish, Angel Garcia-Alonso, Marianne Nicolson, William Steward, Alan Anthoney, R3 최인승/ Pf. 동석호

Introduction The outcome of patients with advanced pancreatic cancer remains poor. less than 12 months During repeated rounds of DNA replication, the telomeric ends of DNA become progressively shortened 아시다시피 advanced pancreatic Ca.의 예후는 12개월 미만으로 여전히 poor하여 새로운 약제가 필요한 시점입니다. Chromosome의 말단에는 TTAGGG 서열이 반복되는 telomere라는 site가 존재하고 DNA가 replication이 되는 동안 이 telomere는 짧아지게 됩니다.

Introduction The outcome of patients with advanced pancreatic cancer remains poor. less than 12 months During repeated rounds of DNA replication, the telomeric ends of DNA become progressively shortened Reactivation of telomerase, the telomere-repair enzyme, is a crucial event in oncogenic transformation, and occurs in nearly all pancreatic cancers

Introduction GV1001 is a human telomerase reverse transcriptase catalytic subunit (hTERT) class II 16mer peptide vaccine

Introduction GV1001 is a human telomerase reverse transcriptase catalytic subunit (hTERT) class II 16mer peptide vaccine A phase 2 trial of GV1001 in advanced pancreatic cancer showed a total immune response in 24 of 38 patients (63%) Immune responders had a greater median survival (216 days) than did non-responders (88 days) The TeloVac study aimed to exploit the positive immunomodulatory effects and tested the effect of combining them with GV1001 with standard chemotherapy Chemotherapy delivered after immunotherapy can enhance the effect of immunotherapy by delivering a bolus of tumour antigens and immunostimulatory signals

Methods Study design Multicentre, three-group, open-label, phase 3 randomised controlled trial 51 UK hospital Inclusion criteria Older than 18yrs Histologically or cytologically confirmed locally advanced or metastatic pancreatic ductal adenocarcinoma ECOG performance status 0~2 Adequate end organ function Exclusion criteria RT within the last 4weeks Intracerebral metastases Previous chemotherapy Clinically significant serious not currently controlled on present therapy Concurrent malignancy

Methods

Methods - procedure Chemotherapy alone group Gemcitabine : 1000 mg/m2, 30 min IV infusion on days 1, 8, and 15 Capecitabine : 830 mg/m2 orally twice daily for 21 days Repeated every 28 days for six cycles, or until disease progression Sequential chemoimmunotherapy group Two cycles of combination chemotherapy Subsequently immunised with an intradermal injection of recombinant GM-CSF (75 μg) into the lower abdomen 10–15 min later, received an intradermal injection at the same site of 0.56 mg of GV1001 (200 mL of 2.8 mg/mL) On days 1, 3, and 5 during week 1, then once on weeks 2, 3, 4, and 6 Concurrent chemoimmunotherapy Received chemotherapy as chemotherapy alone group for 6 cycles GM-CSF and GV1001 from day 1 of therapy Then received just immunotherapy at the end of cycle six https://www.lctu.org.uk/trial/trial_links.asp?id=42&tgcode=-4&menuid=43

Results

Results

Results

Results

Conclusion Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy.

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