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Lunch & Poster Display session

24P - Multiple KRAS mutations detected by cancer related DNA in patients with resected pancreas adenocarcinoma during treatment with TG01/GM-CSF and gemcitabine (CT TG01-01)

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Daniel Palmer

Citation

Annals of Oncology (2019) 30 (suppl_11): xi1-xi11. 10.1093/annonc/mdz447

Authors

D. Palmer1, A. Møller2, B. Greenhalf3, Y.T. Ma4, J.W. Valle5, T.J. Gjertsen2, L. Kuryk6

Author affiliations

  • 1 Molecular And Clinical Cancer Medicine, University of liverpool cancer research UK center, L69 3GA - liverpool/GB
  • 2 Clinical Science, Targovax, 0283 - Oslo/NO
  • 3 Molecular And Clinical Cancer Medicine, University of Liverpool, L69 3GE - Liverpool/GB
  • 4 Institute Of Immunology And Immunotherapy, Queen Elizabeth University Hospital, B15 2TT - Birmingham/GB
  • 5 The Christie Nhs Foundation Trust, University of Manchester, M20 43 X - Manchester/GB
  • 6 Clinical Science, Targovax, 0283 - Oslo/FI
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Resources

Abstract 24P

Background

TG01/GM-CSF is an injectable antigen-specific cancer immunotherapy targeted to treat patients (pts) with KRAS mutations, found in > 90% of pancreatic adenocarcinomas (PAC). TG01 consists of a mixture of 7 synthetic peptides representing 7 of the most common codon 12 and 13 mutations associated with PAC. Pancreatic cancer is a heterogeneous and genetically unstable disease, meaning that more than one KRAS mutation may be present in a single tumor. We investigated if cancer-related DNA from pts with resected PAC had more than one KRAS mutation and if the mutation status changed during treatment with TG01/GM-CSF.

Methods

Pts were eligible after an R0 or R1 PAC resection. TG01 (0.7 mg intradermal injection id) together with GM-CSF (0.03 mg id) was given on day 1, 3, 5, 8, 15, 22 and 2-weekly until end of chemotherapy, 4-weekly up to 1 year and 12-weekly up to 2 yrs. Within 12 weeks after resection, pts were expected to receive gemcitabine for 6 cycles. Plasma samples (up to 9) from 21 pts were collected and cancer related KRAS DNA were analyzed using ARMS (real time qPCR) for the 6 most common mutations: 12D, 12V, 12A, 12R, 12S and 12C.

Results

21 pts from UK, median age 65 (46-77) enrolled between Jan-2014 and Apr-2016. Previous results from tumor specimen showed that 16 out of 21 pts had a KRAS mutation (single mutation). However, when analyzing mutations using ARMS 20 out of 21 pts had ≥1 KRAS mutations; 19 out of 21 pts (90%) had between 1-6 mutations throughout the study. 12D and 12V mutations co-occurred in 17 out of 21 (81%) of the pts. In one pt all 6 assessed KRAS mutations were detected throughout the study. In 5 pts mutations disappeared during the treatment while in 10 pts the mutations changed either revealing new mutations or shift of mutations over time, possibly indicating selection pressure.

Conclusion

The great majority of patients with PAC have multiple KRAS mutations; in addition, mutations changed during the course of the study. Single mutation vaccines and small molecules targeting single mutations are therefore unlikely to be effective while therapies targeting a mix of KRAS mutations (TG01) may be more beneficial.

Clinical trial identification

CT TG01-01; EudraCT: 2012-002400-40.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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