Research projects presented at the Molecular targets and cancer therapeutics congress

Three research projects were elected for poster presentation at the Molecular targets and cancer therapeutics congress 2023 in Boston, USA. The studies are highly relevant for our work at the Phase 1 Unit and the use of genomic profiling in cancer patients. The studies were conducted and presented by two PhD students at the Phase 1 unit, Rigshospitalet, Denmark: Laila Belcaid and Cecilie Iden.

20. November 2023, at 13:58

Copenhagen Prospective Personalized Oncology (CoPPO) – The utility of using genomic profiling for tailored therapy in a Phase 1 setting

In recent years, targeted therapy based on the molecular characterization of tumors has been among the most remarkable advances in cancer medicine. We reported the impact of 10 years of comprehensive genomic profiling in patients with advanced solid tumors at the Phase 1 unit, Department of Oncology, Rigshospitalet, Denmark.

More than 2000 patients with advanced cancer and exhausted treatment options were enrolled. Genomic profiles were obtained in 87% patients. Overall, 24% were treated with targeted therapy. Out of the patients treated with targeted therapy 24% had objective response rate (defined as at least 30% reduction of tumor). This large-scale study demonstrates that genomic profiling is efficient to identify actionable targets and to match patients to targeted therapies.

Conducted and presented by Laila Belcaid

Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting

Genomic profiling (GP) has revolutionized personalized cancer therapy, enabling tailored treatment strategies based on individual tumor characteristics. However, despite its widespread use, there are instances where GP fails. Understanding the causes of such failures is important for improving the success rate of GP.

More than 2000 patients with advanced cancers and exhausted or almost exhausted treatments options were enrolled in the study. GP was unsuccessful in 281 patients (13%). Furthermore, our analysis illustrated that 74% of GP failures were attributable to pre-analytical factors, primarily related to performance status decline. These findings underscore the need for careful patient selection considering the risk of rapidly declining performance status and suggest that performing the biopsy and GP in earlier treatment lines, could significantly improve the success rate of GP.

Conducted and presented by Cecilie Iden and Laila Belcaid

Tumor fraction as a predictive factor of outcome of patients referred for oncology early phase clinical trials: Analyses of two precision medicine studies

Modern phase I trials have rapidly developed during the last decade with encouraging

response rates, leading to a higher demand for enrollment in Phase I trials. However, a worrying 15-20% succumb within 90 days of inclusion, which challenges determining which patients should be offered entry.

The quantification of circulating tumor DNA (ctDNA) shed by measuring tumor fraction (TF) has been associated with prognosis in solid tumors patients. However, whether TF might also be predictive of clinical benefit of systemic treatments in patients referred for early phase studies has remained unknown. Patients were included in two ongoing precision medicine studies (STING, NCT04932525, sponsor: Gustave Roussy; BIP, NCT02534649, sponsor: Institut Bergonié). The study included more than 1000 patients and demonstrated for the first time, to our knowledge, that high TF is significantly associated with worse progression free survival and objective response/stable disease rate. Altogether, our results strongly support TF as being used for informed decision making for patients before participating in phase I trials.

Conducted and presented by Laila Belcaid