FolRα-targeting antibody drug conjugate shows promise in recurrent epithelial ovarian cancer

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Published: 5 Jun 2023
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Dr Ana Oaknin - Vall d´Hebron Institute of Oncology, Barcelona, Spain

Dr Oaknin talks to ecancer at ASCO 2023 about a global study designed to evaluate the efficacy and safety of the novel FolRα-targeting antibody drug conjugate luveltamab tazevibulin in patients with recurrent epithelial ovarian cancer with identified expression levels of folate receptor alpha (FolRα) higher than 25%.

The study shows that luvelta provided a really compelling clinical activity with an overall response rate of 32% in all patients, regardless of folate receptor alpha expression.

The safety profile of this treatment was also quite good because the rate of discontinuation due to adverse events was only 6.8%. 

Dr Oaknin notes that the results support further clinical evaluation. Led by VHIO investigators in Europe, a global phase II/III study is already planned to evaluate this novel ADC in this patient population.

Read more here.
 

My study, our study, is a phase I dose expansion cohort in patients with recurring epithelial ovarian cancer analysing the activity of a new ADC, that is to say antibody-drug conjugate, in patients with ovarian cancer relapse. So what we have done in the study is try to analyse the activity of our new ADC called luveltamab, luvelta as I will now refer to it, in two different doses. One is the lower dose that is 4.3mg/kg every three weeks and the other is the higher dose, 5.2mg/kg. The key point of our study is this ADC is targeting folate receptor alpha. The main characteristic of our ADC is that we enrolled patients regardless of folate receptor alpha expression. What that means is that our target is able to cover a wide ovarian cancer population. 

What we observed with the study is that luvelta provided a really compelling clinical activity with an overall response rate of 32% in all patients, that is to say regardless of folate receptor alpha expression. Then when we look at the patients whose tumours harbour a TPS, tumour proportion score, for folate receptor alpha expression greater than 25%, the overall response rate was even higher, it was 37%. 

But what else we have analysed in our study, we have seen that patients seem to get a deeper antitumour activity when they receive the starting doses of 5.2mg, the higher dose. In addition, we have learned that although our patients need a dose reduction they were able to maintain the initial partial response.

So, in summary, in terms of activity, this new ADC, luveltamab, showed compelling activity in all patients with recurring epithelial ovarian cancer, regardless of folate receptor alpha expression. What about the safety? The safety profile was quite good because the rate of discontinuation due to adverse events was only 6.8%, which means only three patients. In addition, when we analysed the treatment emergent adverse events, the most frequent were neutropenia, nausea, fatigue and arthralgia.

How can these results impact the treatment of epithelial ovarian cancer in the future?

Recurring epithelial ovarian cancer, when the patients became resistant to platinum therapy, is really an unmet clinical need. Until now, the only option that we have was single agent chemotherapy or bevacizumab anti-VEGF therapy plus chemotherapy. Now with this new ADC, with this new targeted therapy, we are broadening the options for our patients. Because, although this is an early development, it’s a phase I trial, the responses that we have seen are very promising. I think we are adding new therapeutic approaches for this group of patients.