DiviTum Clinical Studies

Growing body of evidence

Biovica has successfully worked to realize its vision for DiviTum® by initiating collaborations with globally-renowned research institutes such as the Karolinska Institute and the Dana Farber Cancer institute, as well as the International Breast Cancer Study Group (IBCSG) and the Breast International Group (BIG). As a result, evidence demonstrating that the company’s DiviTum® thymidine kinase-1 (TK) biomarker assay does provide important clinical data in cancer therapy continues to accumulate.

To date, there are twelve published clinical studies documenting DiviTum® in applications to predict and monitor response to therapeutic tumor interventions. For example, one recent study to investigate the clinical relevance of serum TK activity in women with advanced breast cancer prior to treatment found that high TK activity predicted shorter progression-free and overall survival (Bjohle J et al 2013).

Ongoing clinical trials

In addition, Biovica is currently engaged in several clinical studies designed to generate high-impact, high-quality clinical data on the performance of DiviTum® with a number of different solid tumor types and cell-cycle regulating drugs.

Trial of CDK4/6 Inhibitors

In December 2016 at the San Antonio Breast Cancer Symposium, the leading breast cancer conference in the world, the first results of DiviTum® as a tool for evaluating the efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitors were presented. Conducted by Dr Cynthia Ma, University of Washington, St Louis, the study demonstrated a significant correlation and effect of palbociclib (Ibrance®), the first-in-class of CDK4/6 inhibitors, on TK in 50 women with stage II or III hormone-receptor-positive breast cancer. Serum TK activity could also predict tumor Ki67 (increase/decrease) induced by palbociclib, providing the first evidence that DiviTum® has the potential to be used as a liquid form of Ki-67 measuring cell proliferation (sensitivity/specificity; 94.12% and 84% respectively, p<0.05). Serum TK activity may thus serve as a pharmacodynamic marker of CDK4/6 inhibition. Since there are no other efficacy markers for CDK4/6 inhibition today, and no liquid markers correlating to Ki-67 (a common marker for measuring cell proliferation using tumor tissue), this gives DiviTum® unique features.

“Our study provides the first clinical evidence of a method, DiviTum®, for palbociclib treatment effect in breast cancer. The results are very promising and support future studies of DiviTum™ to evaluate and identify patients for response to CDK 4/6 inhibitors,” says Dr Cynthia Ma, MD, PhD, Associate Professor of Medicine, Washington University School of Medicine, St Louis, US.

The PYTHIA study

PYTHIA is a single arm, Phase II clinical trial by IBCSG/BIG. It will follow 120 post-menopausal women with hormone-receptor-positive advanced breast cancer being treated with fulvestrant (Faslodex®) anti-hormonal therapy in combination with the CDK4/6 inhibitor palbociclib (Ibrance®). Specifically, PYTHIA aims to evaluate palbociclib in combination with fulvestrant to assess the association of the primary endpoint progression-free survival with potential biomarkers.

DiviTum® is used to measure TK levels in blood taken from patients before and during therapy to explore whether the assay results can assist physicians in predicting which patient will respond to therapy, as well as in monitoring drug efficacy during treatment.

“We want to explore the potential of DiviTum® to identify those breast cancer patients with a higher likelihood of response to palbociclib. We will also use DiviTum® to monitor patients while on treatment with palbociclib with the aim of testing whether this could be proposed as a new biomarker of treatment efficacy”.
Dr Luca Malorni, MD, PhD, Principal Investigator of the PYTHIA study, Prato Hospital, Italy.

Dana Farber Cancer Institute, Boston, USA

Serum TK activity is also being evaluated as a biomarker for CDK4/6 inhibitor efficacy at the Dana Farber Cancer Institute, which has included DiviTum® in a clinical trial to analyze serum from 139 patients with late-stage metastatic or unresectable lung cancer or KRAS mutation-positive solid tumors.

The study will evaluate new, specific cell-cycle-dependent CDK4/6 inhibitor drugs in combination with MEK inhibitors. TK activity is being assessed as a marker of disease progression, survival and treatment response. The aim is to demonstrate that DiviTum® can predict response and monitor efficacy before and during treatment with the new drugs, and that TK can serve as a pharmacodynamic marker. Preliminary results are expected in 2017.

“We appreciate this opportunity to test DiviTum® in a clinical study and assess its potential as a serum biomarker. We look forward to the results.”
Dr Geoffrey Shapiro, MD, PhD, Director, Early Drug Development Center, Principal Investigator in the study, Dana Farber Cancer Institute.

Karolinska Institute, Stockholm, Sweden

PREDIX LumA is a state-of-the art Phase II randomized trial evaluating response-guided treatment in luminal A breast cancer at the Karolinska Institute in collaboration with Radiumhemmet, Stockholm. The study will enroll 200 women with hormone-dependent breast cancer being treated with endocrine therapy in combination with the CDK4/6 inhibitor palbociclib (Ibrance®).

DiviTum® will be used to measure tumor proliferation in blood samples taken from patients before and during therapy. The study’s main aims are to identify which women are most likely to respond to treatment and to evaluate therapeutic efficacy during treatment.

“We have chosen to include DiviTum® in the study to see if we can use it as a non-invasive marker of efficacy for this new class of drugs called CDK4/6-inhibitors. This is a very promising group of new drugs, but we lack a reliable marker of tumor proliferation to evaluate and predict efficacy. There is a reasonable potential and scientific rationale that DiviTum® may correlate with the efficacy of these new drugs”.
Thomas Hatschek, lead investigator for the study and Associate Professor, Karolinska Institute.