GV1001 for advanced and/or metastatic pancreatic cancer April 2008 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research
GV1001 for advanced and/or metastatic pancreatic cancer Target group Pancreatic cancer: advanced and/or metastatic in combination with gemcitabine and granulocyte monocyte colony stimulating factor (GM-CSF). Technology description GV1001 (tertomotide) is a peptide vaccine that targets telomerase, which is a ribonucleoprotein complex responsible for providing cancer cells with an unlimited capacity to divide, and is expressed in 85-90% of pancreatic cancers 1. The vaccine is based on telomerase peptides, which stimulate T-cells to destroy cancer cells via recognition of the telomerase target, leaving healthy cells unharmed. It is anticipated that GV1001 be used with adjuvant GM-CSF injections as an addition to standard gemcitabine and capecitabine treatment. GV1001 0.56mg is administered intradermally with multiple injections, over the first 4 weeks and then every 4 weeks. GV1001 is in phase II clinical trials for advanced hepatocellular carcinoma and non-small cell lung cancer. Innovation and/or advantages GV1001 is a new approach to cancer therapy and as an additive therapy may improve survival in this patient group, which has a very poor prognosis. Developer Pharmexa. Availability, launch or marketing dates, and licensing plans: GV1001 has orphan drug status in Europe and the USA for this indication. NHS or Government priority area: This topic relates to the NHS Cancer Plan (2000). Relevant guidance NICE technology appraisal. Gemcitabine for the treatment of pancreatic cancer. 2001 2. Proposed NICE technology appraisal out for consultation. Capecitabine for advanced pancreatic cancer. Pancreatic Section of the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Royal College of Pathologists, Special Interest Group for Gastro- Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. 2005 3. Clinical need and burden of disease Pancreatic cancer is the eighth most common cancer in the UK and the sixth most common cause of death from cancer 4. There were 6,655 patients diagnosed with pancreatic cancer in 2004 in England and Wales 5, and 6,462 registered deaths from pancreatic cancer in 2005 6. The one-year and five-year survival rates for people diagnosed in 2001 were 12-13% and 2% respectively 7. An estimated 80% of patients have locally advanced or metastatic disease at diagnosis. 2
Existing comparators and treatments Gemcitabine IV 5-fluorouracil IV Capecitabine - unlicensed Efficacy and safety Trial code NCT00358566 (PrimoVax) 8 : GV1001 with gemcitabine vs gemcitabine alone; phase III. NCT00425360 (TeloVac) 9 : Gemcitabine with capecitabine vs gemcitabine, capecitabine, and GV1001 with GM-CSF; phase III. Sponsor Pharmexa Liverpool University supported by Cancer Research UK. Status Further enrolment halted early due to Ongoing no survival benefits 10. Location Europe, USA, Australia. UK Design Randomised, controlled. Randomised, controlled. Participants in trial Follow-up Primary outcome Secondary outcomes Results Expected reporting date n=360 (520 planned); adults 18 to 75 years; pancreatic cancer; advanced, unresectable. Randomised to: 1. Gemcitabine. 2. GV1001 0.56mg on days 1, 3, 5, 8, 15 and 22, and every 4 weeks thereafter with gemcitabine added at time of first progression. After completion of study treatment, patients followed up every 3 months. Overall survival (OS). n=1100; adults >18 years; pancreatic cancer; advanced, unresectable. Randomised to: 1. Gemcitabine on days 1, 8 and 15 with capecitabine twice daily on days 1-21. Treatment repeated every 4 weeks. 2. Gemcitabine with capecitabine as in arm 1. Treatment repeated every 4 weeks for 2 courses. GM-CSF with GV1001 administered on days 1, 3 and 5 in week 9; once a week in weeks 10-12 and 14; then once a month. 3. Gemcitabine with capecitabine as in arm 1. GM- CSF with GV1001 administered on days 1, 3 and 5 in week 1; once weekly in weeks 2-4 and 6; then once a month. After completion of study treatment, patients followed up every 3 months. OS Progression free survival (PFS); PFS; QOL; efficacy and safety. adverse events; quality of life (QOL); immune response. Preliminary data based on 174 patient - deaths, showed that survival was no better in GV1001 group in which gemcitabine chemotherapy was added to GV1001 only after first progression of disease (arm 2), compared to group that received standard gemcitabine chemotherapy immediately (arm 1). - Expected completion: 2013. Estimated cost and cost impact The cost of GV1001 has not been determined. 3
Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased survival Other: Improved quality of life for patients and/or carers None identified Services Increased use therapy Service reorganisation required Staff or training required administration, management of adverse effects Decreased use Other: Non identified Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Increased costs: capital investment needed New costs: additive costs Savings: Other: References 1 Bernhardt SL, Gjertsen MK, Trachsel S et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study. British Journal of Cancer. 2006; 95(11):1474-82. 2 National Institute for Health and Clinical Excellence (NICE). Pancreatic Cancer Gemcitabine. Technology appraisal 25. May 2001 3 Pancreatic Section of the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Royal College of Pathologists, Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut 2005;54:1-16 4 Ward S, Morris E, Bansback N et al. A rapid and systematic review of the clinical effectiveness and costeffectiveness of gemcitabine for the treatment of pancreatic cancer. Health Technology Assessment. 2001;5:24. Available at: http://www.ncchta.org/execsumm/summ524.shtml (Accessed 9/4/08). 5 Cancer Research UK, Cancer incidence stats. Available at: http://info.cancerresearchuk.org/cancerstats /incidence/site/?a=5441 (Accessed 9/4/08). 6 Cancer Research UK, Cancer mortality stats. Available at: http://info.cancerresearchuk.org/cancerstats /mortality/siteandukcountry/?a=5441 (Accessed 9/4/08). 7 Cancer Research UK, Cancer survival stats. Available at: http://info.cancerresearchuk.org/cancerstats /survival/siteandsex/?a=5441 (Accessed 9/4/08). 8 ClinicalTrials. GV1001 and gemcitabine in sequential combination to gemcitabine monotherapy in pancreatic cancer. Available at: http://clinicaltrials.gov/ct2/show/nct00358566?term=primovax&rank=1 (Accessed 9/4/08). 9 ClinicalTrials. Gemcitabine and capecitabine with or without vaccine therapy in treating patients with locally advanced or metastatic pancreatic cancer. Available at: http://clinicaltrials.gov/ct2/show /NCT00425360?term=Primovax&rank=4 (Accessed 9/4/08). 10 Pharmexa. Pharmexa stops one of two phase III trials. Press release 13 May 2008. Available at: http://www.pharmexa.com/cms/site.aspx?p=74 (accessed 8.8.08) 4
National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0)121 414 7831 Fax +44 (0)121 414 2269 www.pcpoh.bham.ac.uk/publichealth/horizon