TY - JOUR

T1 - ProTarget

T2 - a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling – a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial

AU - Kringelbach, Tina

AU - Højgaard, Martin

AU - Rohrberg, Kristoffer

AU - Spanggaard, Iben

AU - Laursen, Britt Elmedal

AU - Ladekarl, Morten

AU - Haslund, Charlotte Aaquist

AU - Harsløf, Laurine

AU - Belcaid, Laila

AU - Gehl, Julie

AU - Søndergaard, Lise

AU - Eefsen, Rikke Løvendahl

AU - Hansen, Karin Holmskov

AU - Kodahl, Annette Raskov

AU - Jensen, Lars Henrik

AU - Holt, Marianne Ingerslev

AU - Oellegaard, Trine Heide

AU - Yde, Christina Westmose

AU - Ahlborn, Lise Barlebo

AU - Lassen, Ulrik

N1 - Funding Information: The ProTarget trial is funded by the Danish Cancer Society (R270-A15507). Drugs and funding for data handling are supplied by Roche, Pfizer (for avelumab, as part of an alliance between Pfizer and Merck [CrossRef Funder ID: https://doi.org/10.13039/100009945 ]), GSK, and Incyte. ProTarget is an Investigator-Initiated Trial; none of the funders participated in study design or conduct, but eligible molecular alterations as defined in Table were agreed upon between sponsor and each pharmaceutical company. Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30–80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation. Study design/methods: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0–2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon’s two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing. Discussion: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy. Protocol version: 16, 09-MAY-2022. Trial registration: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019–004771-40.

AB - Background: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30–80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation. Study design/methods: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0–2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon’s two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing. Discussion: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy. Protocol version: 16, 09-MAY-2022. Trial registration: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019–004771-40.

KW - Cancer genetics

KW - Cancer immunotherapy

KW - Clinical trials

KW - Precision oncology

KW - Targeted therapies

KW - Tumor-agnostic therapy

U2 - 10.1186/s12885-023-10632-9

DO - 10.1186/s12885-023-10632-9

M3 - Journal article

C2 - 36814246

AN - SCOPUS:85148549306

VL - 23

JO - B M C Cancer

JF - B M C Cancer

SN - 1471-2407

IS - 1

M1 - 182

ER -