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