Abstract 594P
Background
The evolution of genomic profiling and the increasing number of targeted therapies has made precision medicine a pivotal part of cancer treatment. DRUP is an ongoing, multi-drug, pan-cancer precision oncology trial and provides access to FDA/EMA approved targeted and immunotherapies based on the tumour’s molecular profile outside their label (van der Velden et al, Nature 2019). Here, we present the results of the first 500 treated patients.
Methods
Eligible patients with metastatic cancer have exhausted all regular therapies and harbor an actionable target identified by various profiling techniques. Patients are enrolled in parallel cohorts, defined by tumour type, molecular profile and study drug. Primary endpoint is clinical benefit (objective response or stable disease ≥ 16 weeks), analyzed per cohort using Simon’s two-stage design.
Results
Between Sep 2016 and Nov 2019, 500 of 1145 patients reviewed by the central study team initiated treatment with one of 25 study drugs. In 51% the target was identified by whole genome sequencing, the remaining by other tests (i.e. smaller gene panels, FISH). Most frequently reported targets of submitted cases were aberrations of ERBB2 (n = 135), CDKN2A (n = 104) and BRCA1/2 (n = 81), but also mismatch repair deficiency (n = 98) or high mutational load (n = 171). Rarely reported targets were NTRK mutation (n=1), NRG1 fusion (n=1) and PALB2 mutations (n=5). The total number of cohorts (n = 146) has increased by 54% in the last year, largely due to the addition of CDK4/6 inhibitors. Targets most frequently represented in all cohorts were ERBB2 amplification (7%), CDKN2A loss (6%) and FGFR2 alterations (5%). Clinical benefit was observed across all treatment types (immunotherapy 36%; monoclonal antibodies 27%; small molecule / PARP inhibitors 33%). At data cut-off, 5 cohorts were closed to accrual, 2 of which (nivolumab for MSI tumours / olaparib for BRCA mutated tumours) were expanded to a personalized reimbursement stage.
Conclusions
The adaptive character of the DRUP creates ongoing chances for rare subgroups of metastatic cancer patients by prompt implementation of new scientific insights and provides continued access to successful proven drugs in a personalized reimbursement model.
Clinical trial identification
NCT02925234 (release date: 26-Aug-2016).
Editorial acknowledgement
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Clovis Oncology; Eisai; Ipsen; MSD; Novartis; Pfizer; Roche; Hartwig Medical Foundation; Dutch Cancer Society (KWF): Barcode for Life Foundation (BFL).
Disclosure
C. Van Herpen: Advisory/Consultancy, on behalf of institute: Bayer; Advisory/Consultancy, Research grant/Funding (institution), on behalf of institute: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution), on behalf of institute: Ipsen; Advisory/Consultancy, Research grant/Funding (institution), on behalf of institute: MSD; Advisory/Consultancy, on behalf of institute: Regeneron; Research grant/Funding (institution): AstraZenca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Sanofi . H. Gelderblom: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Five Prime; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Debio; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Teva. H.M.W. Verheul: Honoraria (institution), Advisory/Consultancy: Glycostem; Honoraria (institution), Advisory/Consultancy: Lava Therapeutics. All other authors have declared no conflicts of interest.