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Basic science

1080 - Expanding the use of approved drugs: The CPCT’s Drug Rediscovery Protocol (DRUP) (2O)

Date

17 Nov 2017

Session

Basic science

Presenters

Emile Voest

Citation

Annals of Oncology (2017) 28 (suppl_10): x1-x6. 10.1093/annonc/mdx652

Authors

D. van der Velden1, L. Hoes1, H. Bloemendal2, K. Grunberg3, A.D.R. Huitema4, E. Lugtenburg5, F. De Vos6, C. van Herpen7, D.J.A. de Groot8, P. Hamberg9, E. Smit10, E. Cuppen11, N. Steeghs4, S. Sleijfer12, H. Verheul13, H. Gelderblom14, E. Voest15, H. van der Wijngaart13

Author affiliations

  • 1 Molecular Oncology, Netherlands Cancer Institute, Amsterdam/NL
  • 2 Medical Oncology, Meander Medical Center, Amersfoort/NL
  • 3 Pathology, Radboud University Medical Center, Nijmegen/NL
  • 4 Medical Oncology And Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam/NL
  • 5 Hematology, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 6 Medical Oncology, University Hospital Utrecht, 3508 GA - Utrecht/NL
  • 7 Medical Oncology, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL
  • 8 Medical Oncology, University Medical Center Groningen, Groningen/NL
  • 9 Medical Oncology, Franciscus Gasthuis & Vlietland, 3045 PM - Rotterdam/NL
  • 10 Medical Oncology, Netherlands Cancer Institute, Amsterdam/NL
  • 11 Human Genetics, University Medical Center Utrecht, 3508 GA - Utrecht/NL
  • 12 Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, 3075 EA - Rotterdam/NL
  • 13 Medical Oncology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 14 Medical Oncology, Leiden University Medical Center (LUMC), 2300 RC - Leiden/NL
  • 15 Molecular Oncology, Netherlands Cancer Institute, 1066CX - Amsterdam/NL
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Abstract 1080

Background

Once regulatory drug approval is obtained, patients and pharma would greatly benefit from identifying signals of activity in cancer subsets outside the approved indication. In the Netherlands’ precision oncology-network (www.cpct.nl), Whole Genome Sequencing (WGS) is offered to systemically treated cancer patients. This allows us to identify a spectrum of potentially actionable genetic aberrations in all types of cancer. The DRUP provides patients with such aberrations access to genetically matched treatment upon central review of the tumor profile.

Methods

Adult patients with solid tumors, glioblastoma, lymphoma or multiple myeloma, with no standard treatment options, are eligible. Patients are enrolled in multiple parallel cohorts, each defined by 1 tumor type, 1 tumor profile and 1 treatment. Efficacy is analyzed per cohort using a Simon-2-stage approach, aimed at ≥ 1 clinical benefit (CR, PR or SD ≥ 16 weeks)/8 patients in stage I, and ≥5/24 in stage II (85% power, α error rate 7.8%). A fresh tumor biopsy for biomarker research is mandatory. There are currently 23 participating hospitals and 19 study drugs, supplied by 10 pharmaceutical companies.

Results

Since study launch Sep 2016, 200 cases were submitted for review and 60 patients started treatment. Clinical benefit was observed in 37% (6% CR, 14% PR, 17% SD ≥ 16 weeks; all CRs and 2/3 of PRs were ongoing at the time of writing and awaiting ≥30 days confirmation). About 2/3 of case submissions were rejected, due to a general protocol ineligibility (18%), b current unavailability of matching study drugs (17%), c no actionable target detected (15%), d negative evidence for target-drug-match (13%), e eligible for standard treatment (12%), f eligible for competing trials (11%), g loss to follow up (10%) or h genetic tumor profile not yet assessed (4%).

Conclusions

Execution of a national multi-drug and multi-tumor precision oncology trial is feasible. By performing WGS in many different cancer types, subgroups are identified who may benefit from existing drugs outside of their registered indication. This study hereby accelerates translation of new findings to the clinic and increases the yield of existing therapies.

Clinical trial identification

NCT02925234 (release date: 26-Aug-2016) EudraCT 2015-004398-33 (release date: 01-Oct-2015).

Legal entity responsible for the study

Governance: Stichting Het Nederlands Kanker Instituut – Antoni van Leeuwenhoek Ziekenhuis, whose registered office is at Plesmanlaan 121, 1066CX, Amsterdam, lawfully represented by Prof. R. Medema, Head of the Board representing the CPCT. Coordination and running of the study: Prof. E.E. Voest, Netherlands Cancer Institute, division of Molecular Oncology, Amsterdam, the Netherlands.

Funding

Barcode for Life Foundation (BFL): funding • Dutch Cancer Society (KWF): funding • Hartwig Medical Foundation (HMF): sequencing • Pharmaceutical partners (Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Novartis, Roche): funding and study drugs.

Disclosure

F. De Vos: Direct research support to the responsible project lead (PI): Array, AstraZeneca, BMS, GSK, Merck, Merus, Novartis, Roche/Genentech, E. Cuppen: Board of directors of Hartwig Medical Foundation (not for profit), N. Steeghs: Consulting or advisory role: Lilly Research funding: AB Science, AstraZeneca, Bayer, Boehringer Ingelheim, BristolMS. All other authors have declared no conflicts of interest.

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