The Drug Rediscovery Protocol (DRUP Trial)

Summary

This is a prospective, non-randomized clinical trial that aims to describe the efficacy and toxicity of commercially available, targeted anticancer drugs\* prescribed for treatment of patients with advanced cancer with a potentially actionable variant as revealed by a genomic or protein expression test. The study also aims to simplify patient access to approved targeted therapies that are contributed to the program by collaborating pharmaceutical companies and to perform next generation sequencing on tumor biopsies for biomarker analyses. Eligible patients have an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma for which standard treatment options are no longer available and acceptable performance status and organ function. A genomic or protein expression test must have been performed on the tumor and the results must identify at least one potentially actionable molecular variant as defined in the protocol. Results from the molecular profiling test will be used to determine an appropriate drug(s) from among those available in the protocol. The choice of drug will be supported by a list of potential profiles, a molecular tumor board, a knowledge library and by study coordinators for review and approval of the match. The protocol-specified treatment will be administered to the patient once any drug-specific eligibility criteria are confirmed and a fresh pre-treatment biopsy is performed for future genetic studies. All patients who receive treatment with a drug available in the protocol will be followed for standard efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment. In addition, treatment related toxicity will be evaluated.

Timeline

Start

2016-08

Primary completion

2027-09

Completion

2027-12

Outcome

Mixed primary results

paper Although pembrolizumab lacked activity in cohort A, cohorts B and C met the study's primary endpoint. PMID 38630551 ↗

Publications

• Verkerk K, Spiekman AC, Haj Mohammad SF, Verbeek FAJ, Timmer H, van Maren MA, Zeverijn LJ, Geurts BS, van der Noort V, Roepman P, Jansen AML, de Leng WWJ, Gelderblom H, Verheul HMW, Voest EE; DRUP Trial Investigators. Prospective evaluation of genomics-guided off-label treatment. Nature. 2026 May;653(8114):558-566. doi: 10.1038/s41586-026-10405-x. Epub 2026 Apr 15.
• Geurts BS, Zeverijn LJ, Leek LVM, van Berge Henegouwen JM, Hoes LR, van der Wijngaart H, van der Noort V, van de Haar J, van Ommen-Nijhof A, Kok M, Roepman P, Jansen AML, de Leng WWJ, de Jonge MJA, Hoeben A, van Herpen CML, Westgeest HM, Wessels LFA, Verheul HMW, Gelderblom H, Voest EE. Efficacy of Pembrolizumab and Biomarker Analysis in Patients with WGS-Based Intermediate to High Tumor Mutational Load: Results from the Drug Rediscovery Protocol. Clin Cancer Res. 2024 Sep 3;30(17):3735-3746. doi: 10.1158/1078-0432.CCR-24-0011.
• Zeverijn LJ, Looze EJ, Thavaneswaran S, van Berge Henegouwen JM, Simes RJ, Hoes LR, Sjoquist KM, van der Wijngaart H, Sebastian L, Geurts BS, Lee CK, de Wit GF, Espinoza D, Roepman P, Lin FP, Jansen AML, de Leng WWJ, van der Noort V, Leek LVM, de Vos FYFL, van Herpen CML, Gelderblom H, Verheul HMW, Thomas DM, Voest EE. Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials. Int J Cancer. 2023 Oct 1;153(7):1413-1422. doi: 10.1002/ijc.34649. Epub 2023 Jul 10.
• Geurts BS, Battaglia TW, van Berge Henegouwen JM, Zeverijn LJ, de Wit GF, Hoes LR, van der Wijngaart H, van der Noort V, Roepman P, de Leng WWJ, Jansen AML, Opdam FL, de Jonge MJA, Cirkel GA, Labots M, Hoeben A, Kerver ED, Bins AD, Erdkamp FGL, van Rooijen JM, Houtsma D, Hendriks MP, de Groot JB, Verheul HMW, Gelderblom H, Voest EE. Efficacy, safety and biomarker analysis of durvalumab in patients with mismatch-repair deficient or microsatellite instability-high solid tumours. BMC Cancer. 2023 Mar 4;23(1):205. doi: 10.1186/s12885-023-10663-2.
• van Berge Henegouwen JM, van der Wijngaart H, Zeverijn LJ, Hoes LR, Meertens M, Huitema ADR, Devriese LA, Labots M, Verheul HMW, Voest EE, Gelderblom H. Efficacy and toxicity of vemurafenib and cobimetinib in relation to plasma concentrations, after administration via feeding tube in patients with BRAF-mutated thyroid cancer: a case series and review of literature. Cancer Chemother Pharmacol. 2022 Jul;90(1):97-104. doi: 10.1007/s00280-022-04437-z. Epub 2022 May 22.
• Nakauma-Gonzalez JA, Rijnders M, van Riet J, van der Heijden MS, Voortman J, Cuppen E, Mehra N, van Wilpe S, Oosting SF, Rijstenberg LL, Westgeest HM, Zwarthoff EC, de Wit R, van der Veldt AAM, van de Werken HJG, Lolkema MPJ, Boormans JL. Comprehensive Molecular Characterization Reveals Genomic and Transcriptomic Subtypes of Metastatic Urothelial Carcinoma. Eur Urol. 2022 Apr;81(4):331-336. doi: 10.1016/j.eururo.2022.01.026. Epub 2022 Jan 25.

Drugs

Indications