Medicine Matters oncology

At San Antonio, we are going to be presenting the data from the ASCENT clinical trial, in particular data relating to the biomarker analysis. So the ASCENT clinical trial was a phase 3 randomized study evaluating sacituzumab govitecan, an anti-Trop2 antibody drug conjugate, versus single agent chemotherapy of physician's choice for patients with metastatic triple negative breast cancer who had received at least two prior lines of therapy in the metastatic setting.

This study's original efficacy analysis was presented at ESMO 2020 showing a significant improvement in PFS, as well as overall survival for patients treated with sacituzumab govitecan. This ultimately securing the availability of this drug for patients with third-line metastatic triple negative breast cancer. It is FDA approved in the US based on the promising early phase study. And these data did confirm those very promising findings.

So the Trop-2 antigen that this antibody drug conjugate is targeting is actually pretty widely expressed in breast cancers, and has been associated with poor outcomes for patients who do have tumor expression of this antigen. And so our analysis wanted to look at the level of Trop-2 expression on cancer cells and see if there was a correlation between level of antigen expression and efficacy from sacituzumab govitecan.

So the expression level was measured on a proportion of patients using archival tumor tissue. Not all patients had the tumor tissue available, but it was for a large number of patients. The Trop-2 expression was known for about 60% of patients in each arm.

And we divided it based on low expression based on an H score, low expression, medium expression, or high expression of Trop-2. And then we looked at the progression-free survival and overall survival outcomes based on the level of expression.

And for each level, each group level, SG outperformed the standard of care arm in terms of both median progression-free survival and overall survival, and in fact objective response rate. So regardless of whether a patient had low Trop-2, medium Trop-2, or high Trop-2 tumor expression, they did better with sacituzumab than with treatment of physician's choice.

Another interesting finding is that patients tended to do better, period, with medium or high levels of Trop-2 expression. We also looked at BRCA mutation analysis. So again, somewhere around a third of patients did have a known BRCA, one or two mutation status, and around 7% or 8% of patients did have BRCA mutation in this analysis.

And the numbers were kind of small. However, reassuringly, patients did derive benefit from sacituzumab govitecan compared to treatment of physician's choice, whether or not they were BRCA I or II carrier. So if the patient was not a BRCA carrier, they had a better objective response, progression-free survival and overall survival, compared to treatment of physician's choice. And if they were a BRCA carrier, again, patients treated with sacituzumab did better than with treatment of physician's choice.

So very reassuring exploratory analyses, but reassuring results indicating that we haven't found a patient type based on trope expression or based on BRCA mutation analysis who wouldn't benefit from sacituzumab.

The ASCENT study was conducted in pretty late-line setting. Patients had been treated with at least two lines of therapy. And many patients had many more lines of therapy than that in the metastatic setting. And so it secured its place in the late line setting for metastatic triple negative breast cancer.

But we are eager to see what the efficacy of this molecule is like in earlier line settings-- first line, second line setting in triple negative breast cancer. Also, looking forward to seeing data relating to its use in the other tumor subtypes-- for example, hormone receptor positive, HER2 negative metastatic breast cancer, and actually in the neoadjuvant and adjuvant setting.

So I think there are a number of studies being planned or discussed, and the number of ongoing studies to evaluate sacituzumab in each of these ways.