Phase II Topology Trial for PLX038 in Triple-Negative Breast Cancer at Institut Curie

ProLynx Inc. has initiated a Phase II clinical trial known as TOPOLOGY, which is focused on the investigation of a drug called PLX038 for the treatment of triple-negative breast cancer (TNBC). This trial marks a significant step in the study of this condition, which has limited treatment options, particularly for those whose cancer has not responded to standard therapies.

The trial is noteworthy for its innovative approach to drug delivery. PLX038 is a prodrug of SN-38, a compound that inhibits topoisomerase 1, an enzyme crucial for DNA replication. By targeting this enzyme, PLX038 can induce DNA breaks that lead to the death of cancer cells, particularly those that are deficient in DNA repair mechanisms. The drug is designed to be slowly released from a nanoparticle carrier, which allows for a sustained presence of SN-38 in the body, potentially increasing both the safety and effectiveness of the treatment.

Previous research has indicated that approximately one-third of TNBC patients have a compromised ability to repair DNA damage, suggesting that they may be particularly responsive to therapies like PLX038. Moreover, the drug has been shown in preclinical studies to accumulate within solid tumors, where it can exert its therapeutic effects.

The trial is being conducted by Institut Curie, a leading cancer research and treatment center in France, under the guidance of principal investigator Prof. Francois-Clement Bidard. The study will assess the efficacy of PLX038 in patients who have previously been treated with at least two different therapies, including sacituzumab govitecan, an antibody-drug conjugate that also delivers SN-38.

One of the key aspects of the TOPOLOGY trial is its focus on identifying biomarkers that can predict a patient's response to PLX038. By examining the correlation between the drug's efficacy and specific genetic defects or biomarkers, such as SFLN11 expression and RB1 loss, the trial aims to enable the pre-selection of patients who are most likely to benefit from the treatment.

ProLynx's co-founder and President, Daniel V. Santi, has highlighted the unique anti-tumor mechanisms of PLX038 compared to other drugs that use the same active ingredient, suggesting that it may be effective against tumors that have become resistant to existing treatments.

The TOPOLOGY trial represents a promising development in the ongoing battle against TNBC, offering hope for patients who have exhausted other treatment options. The innovative approach to drug delivery and the potential for personalized medicine, through the identification of predictive biomarkers, underscores the importance of continued research and development in the field of oncology.