Antineoplastic Agents

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Anti-Arrhythmia Agents

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Amino Acids

Trastuzumab

Niraparib

Avelumab

Axitinib

Atezolizumab

Alectinib

Pertuzumab

Ado-Trastuzumab Emtansine

Erlotinib Hydrochloride

Vemurafenib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Tubulin Modulators

Antimitotic Agents

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Immunologic Factors

Tyrosine

Alectinib for patients with a molecular tumor profile that can potentially be targeted by Alectinib.

Atezolizumab for patients with a molecular tumor profile that can potentially be targeted by Atezolizumab.

Avelumab for patients with a molecular tumor profile that can potentially be targeted by Avelumab.

Axitinib for patients with a molecular tumor profile that can potentially be targeted by Axitinib.

Erlotinib for patients with a molecular tumor profile that can potentially be targeted by Erlotinib.

Vemurafenib plus Cobimetinib (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Vemurafenib plus Cobimetinib.

Trastuzumab plus Pertuzumab (combination treatment) for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab plus Pertuzumab.

Trastuzumab emtansin for patients with a molecular tumor profile that can potentially be targeted by Trastuzumab emtansin.

Vismodegib for patients with a molecular tumor profile that can potentially be targeted by Vismodegib.

Niraparib for patients with a molecular tumor profile that can potentially be targeted by Niraparib.

Alectinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Alectinib might be expected based on their molecular tumor profile.

Atezolizumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Atezolizumab might be expected based on their molecular tumor profile.

Avelumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Avelumab might be expected based on their molecular tumor profile.

Axitinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Axitinib might be expected based on their molecular tumor profile.

Erlotinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Erlotinib might be expected based on their molecular tumor profile.

Erlotinib

Vemurafenib plus Cobimetinib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Vemurafenib plus Cobimetinib might be expected based on their molecular tumor profile.

Vemurafenib plus Cobimetinib (combination)

Trastuzumab plus Pertuzumab treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Trastuzumab plus Pertuzumab might be expected based on their molecular tumor profile.

Trastuzumab plus Pertuzumab (combination)

Trastuzumab emtansine treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Trastuzumab emtansine might be expected based on their molecular tumor profile.

Trastuzumab emtansine

Vismodegib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Vismodegib might be expected based on their molecular tumor profile.

Vismodegib

Niraparib treatment for patients with an advanced solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma, who are not eligible for on-label treatment but for whom anti-tumor activity of Niraparib might be expected based on their molecular tumor profile.

Ulrik Lassen, Prof.

Kristoffer S Rohrberg, MD, PhD

Morten Ladekarl, MD, Prof.

Britt E Laursen, MD, PhD

Rikke L Eefsen, MD, PhD

Karin Holmskov, MD

Julie Gehl, MD

Lars H Jensen, MD, PhD

The ProTarget study is a phase II, prospective, non-randomized clinical trial with the primary purpose of investigating the safety and efficacy of commercially available cancer drugs that target specific changes in cancer cell DNA to treat patients with advanced cancer. The primary endpoint is anti-tumor activity or stable disease documented after 16 weeks of experimental drug treatment. The drugs used in the trial have been approved by EMA/FDA for the treatment of certain cancers. Choice of drug is based on whether the patient's cancer cells contain precisely the DNA change (i) targeted by the EMA/FDA-approved drug or (ii) related to sensitivity to the EMA/FDA-approved drug. The trial drug is thus not approved by the EMA/FDA or in Denmark for the treatment of the patient's cancer - it is so-called "off-label use". The secondary purposes are:

* To detect side effects in patients treated with commercially available targeted cancer drugs.
* Performing biomarker analyzes, including (but not limited to) whole-genome analysis (WGS) on a fresh tumor tissue sample (biopsy) at baseline and progression.
* To investigate mechanisms of resistance using recurrent / serial fresh tumor biopsies for WGS and so-called liquid biopsies, which are blood samples in which the cancer cell DNA is analyzed.

The secondary endpoints include response duration, progression-free survival, and overall survival.

The ProTarget study is a phase II, prospective, non-randomized clinical trial that aims to describe the safety and efficacy of commercially available, targeted anti-cancer drugs prescribed for treatment of patients with advanced cancer having a potentially actionable genomic variant revealed by a genomic test or immunohistochemistry test for protein overexpression performed in a laboratory accredited by the competent local regulatory authority. The study also aims to catalogue the choice of genomic test by clinical oncologists and learn about the utility of data collected through this study to develop hypotheses for future clinical trials. Eligible patients will have an advanced malignant disease with molecular aberrations for which standard treatment options are no longer available or feasible and acceptable performance status and organ function. A genomic test or immunohistochemistry test for protein overexpression must have been performed on a specimen of the tumor selected by the investigator in a laboratory accredited by the competent local regulatory authority and the test must identify at least one potentially actionable genomic variant as defined in the protocol. Genomic assays performed on cell-free DNA in plasma or other body fluids ("liquid biopsies") will also be acceptable if the genomic analysis is performed in a laboratory that meets the requirements described above. The investigator will select an appropriate drug from among those available in the protocol that targets the identified genomic variant and begin treatment once any drug-specific eligibility criteria are confirmed. If an eligible drug-variant match is not listed in the protocol, the physician may submit a proposal to treat with a drug available in the protocol, along with relevant clinical information and the genomic test results, to the study Molecular Tumor Board for review. The investigator may also choose to request options from the Molecular Tumor Board on treatment selection. The Molecular Tumor Board will return to the physician a list of potential treatment options. If the physician's choice of drug is among those available in the protocol and also one of the options provided by the Molecular Tumor Board, the protocol-specified treatment may be administered to the patient once any drug-specific eligibility criteria are confirmed. The investigator may not enroll a patient on a ProTarget study drug if it is not among the options listed in the protocol or provided by the Molecular Tumor Board. In this case, the non-ProTarget treatment and follow-up will be at the investigator's discretion. All patients who receive treatment with a drug available in the protocol will be followed for standard toxicity and efficacy outcomes including tumor response, progression-free and overall survival as well as duration of treatment and high grade or serious adverse events.

Study Objectives:

* To describe in different types of population the anti-tumor activity (efficacy) and toxicity (safety) of commercially available, targeted anti-cancer drugs used for treatment of patients with advanced disease with a genomic variant known (i) to be a target of an EMA-approved anti-cancer drug or (ii) to predict sensitivity to an EMA-approved anti-cancer drug.
* To record the site investigator determination treatment-related adverse events experienced by patients receiving treatment with commercially available, targeted anti-cancer drugs.
* To perform refined biomarker analyses, including (but not limited to) whole genome sequencing, on a fresh tumor biopsy specimen at baseline and at progression.
* To study mechanisms of resistance by the use of serial fresh tumor biopsies for WGS and liquid biopsies.

Study Population: Eligible patients will have an advanced malignant disease for which standard treatment options are no longer available or feasible and acceptable performance status and organ function. A genomic profiling test or immunohistochemistry test for protein expression or overexpression must have been performed on a specimen of the tumor in a laboratory accredited by the competent local regulatory authority. The results must identify at least one potentially actionable genomic variant that is targeted by a ProTarget Study drug, as defined in the protocol. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed in a laboratory that meets the requirements described above.

Intervention: Treatment with a commercially available, targeted anti-cancer drug matched to a genomic variant identified in a tumor biopsy specimen.

Study endpoints: Objective tumor response (complete response - CR or partial response- PR) or stable disease (SD) at 16 weeks or later after treatment initiation and safety are the primary study endpoints; progression-free survival, overall survival, duration of treatment on study and treatment-related high grade and serious adverse events will be collected.

Patients from Denmark, the Netherlands and the USA will be included in three similar though independent protocols (ProTarget, DRUP and TAPUR, respectively), allowing data-exchange and empowering of the trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling	NCT04341181	Cancer Tumors Neoplasms Neoplasia	Alectinib Atezolizumab Avelumab Axitinib Erlotinib Vemurafenib plu... Trastuzumab plu... Trastuzumab emt... Vismodegib Niraparib	18 Years -	Rigshospitalet, Denmark
ProTarget - A Danish Nationwide Clinical Trial on Targeted Cancer Treatment Based on Genomic Profiling	NCT04341181	Cancer Tumors Neoplasms Neoplasia	Alectinib Atezolizumab Avelumab Axitinib Erlotinib Vemurafenib plu... Trastuzumab plu... Trastuzumab emt... Vismodegib Niraparib	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for trastuzumab plus pertuzumab (combination)