Early Clinical Trials

PCM Task force chair: Claes Karlsson

The objectives are to interact with the corresponding TF of CCE (currently a major focus on the BoB trial) as well as suggest trials to be included in the CCE TF and to seek collaborations in terms of Swedish PCM-trials. Additionally, to interact with other TFs both locally and with CCE for tissue and imaging diagnostics.

Completed activities and achieved results

The most important achievement to date has been the extensive support allowing for incorporation of KI and K in the CCE program. CCE has in turn provided, a much needed, experience in interpreting and discussing the significance of molecular findings in the context of cancer therapies and started the BoB-rial (see below).

Karolinska initiated studies, most of these include in house biomarker studies:

• Adoptive T-cell Phase I (MAT02), a two-step immunotherapy approach consisting of T-cell therapy and dendritic cell vaccine
• The MASTIFF study, a first-in-man and first-in-class study of an MTH-1 inhibitor in solid tumours
• The Pluto study, an umbrella study with approved drugs in lung cancer involving all major centres in Sweden and where cases are treated with targeted agents based on genomic routine information (late planning phase), the study is led by the Stockholm PCM program (dr. Simon Ekman and assembles the Swedish Lung Cancer trial group)
• SBRT consolidation studies (in late planning phase) of targeted therapies and immunotherapy where SBRT is used to eradicate residual metastases post initial treatment
• Dose restriction studies in radiation therapy. Precision oriented dose planning-SBRT.
• Pre-screening for phase-I studies (PSFF project) using a 200 gene in-house panel for liquid biopsies examining ctDNA and germline DNA.

Investigator driven studies (Karolinska active but with leading inst. in brackets) and initiated within Cancer Core Europe:

• The BoB trial (CCE): Atezolizumab – running. Planned: inhibitors of FGFR, ALK-ROS1, MET, SMARCb1, HER2, HRAS, KIT/PDGFRa
• The European DRUP trial (NKI)

Future activities

We are planning on expanding the PSFF project to include transcriptomics, proteomics, cytokine and cyTOF immunoprofiling in patients referred to the phase-I unit. This will be coupled at a later date to the development of ex vivo functional drug testing in solid tumors. Our involvement in CCE will expand and this stimulates translational research as well as offer greater access to clinical trials where patient selection is based on molecular fingerprinting.The use of the MTB portal (which is successfully utilized within the BoB-trial) in various research projects, both within and outside the CCE, will increase.