Copenhagen Prospective Personalized Oncology (CoPPO) - Clinical utility of using molecular profiling to select patients to phase 1 trials.

PURPOSE: We evaluated the clinical benefit of tumor molecular profiling (MP) to select treatment in the phase 1 setting.

EXPERIMENTAL DESIGN: Patients with advanced solid cancers and exhausted treatment options referred to a phase 1 unit were included in a prospective single-centre single-arm open-label study (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis including whole exome sequencing (WES) and RNA sequencing. When possible, patients were treated with regimen matched to the genomic profile. Primary endpoint was progression free survival.

RESULTS: From May 2013 to January 2017 a total of 591 patients were enrolled with 500 patients undergoing biopsy. Genomic profiles were obtained in 460 patients and a potential actionable target was identified in 352 (70%) of 500 biopsied patients. One hundred and one patients (20%) received matched treatment based on either gene mutations or RNA expression levels of targets available in early clinical trials or off-label treatment. Objective response according to RECIST1.1 was observed in 15/101 patients (0% CR, 15% PR) with a median PFS of 12 weeks (95% CI 9.9-14.4).

CONCLUSIONS: Our study supports the feasibility of genomic profiling to select patients in the phase 1 setting and suggests that genomic matching can be beneficial for a minor subset of patients with no other treatment options. Randomized studies may validate this assumption.