Discover the potential of tisotumab vedotin combinations and emerging treatment strategies in the evolving landscape of cervical cancer management.
Ramez N. Eskander, MD: There is ample opportunity to continue to improve the treatment landscape for cervical cancer. I want to build upon the data from innovaTV 204, which led to the accelerated approval in 2021 [and] the press release from the confirmatory trial of innovaTV 301. We also have data from innovaTV 205, which looked at various combinations, which brought the antibody-drug conjugate…can we put tisotumab vedotin, which has a microtubule-disrupting payload, with carboplatin almost as a paclitaxel substitute? Can we combine tisotumab vedotin with immunotherapy, pembrolizumab, understanding that pembrolizumab has efficacy in cervical cancer? But can the combination lead to a provocative signal to inform subsequent trials, or can we give tisotumab with pembrolizumab and carboplatin?
You can imagine an evolution, again, where we’re trying to take away and theoretically replace paclitaxel with the antibody-drug conjugate tisotumab vedotin. And I will tell you that exploratory studies have been conducted looking at these combinations. When you look at frontline tisotumab vedotin plus pembrolizumab, of 32 patients, it’s a small population, 78% of patients that were treated had a reduction in their target lesion size. So, again, it’s a signal, it’s provocative and it’s informative. When we look at second-line or third-line previously treated patients giving tisotumab vedotin plus pembro[lizumab], again, of the entire cohort that was treated, of 34 patients, 74% had some degree of a reduction in their target lesion.
And then in the front line when we combined tisotumab vedotin with carboplatin as a paclitaxel substitute, again, we looked at 33 patients; 85% of those had some reduction in their target lesions on treatment. So, it is exciting, it is informative, it is hypothesis generating so that we can take this information and potentially leverage it to inform future clinical trials looking at combination strategies. And we can also look at the objective response rate for these combinations. So again, if we look at frontline tisotumab plus pembrolizumab, the objective response rate was 40.6%. In the recurrent setting when we gave tisotumab plus pembro[lizumab], 38.2% response rate. And then if we look at the front line of tisotumab plus carboplatin, 54.5% response rate. So, informative in the fact that it helps guide our ability to think about future clinical trials. But again, these were small patient cohorts for each of these combinations and I’m excited to see where the future is going to take us and whether there will be improved outcomes by looking at these novel combinatorial strategies.
It is, in my mind, so important as we enter an era of molecular characterization of disease when we think about all our gynecologic diseases—ovarian cancer, endometrial cancer, cervical cancer—we are continuing to learn more about the relevance of these biomarkers. And so, in the management of cervical cancer, we understand it’s already an uncommon disease. It’s already a disease where…unless you’re at a bigger center that’s a referral center, or as a GYN oncologist, you’re seeing many [patients with cervical cancer], there may be a time where you see only a few of these patients. And so, it’s incredibly important for us to stay informed about what is the evolving landscape of treatment.
We know the relevance of the PD-L1 CPS [combined positive score]. We know the newly approved FDA indication KEYNOTE 826 chemo[therapy] plus pembro[lizumab] with or without bev[acizumab]. We know about pembro[lizumab] monotherapy opportunities. The therapeutic opportunity with tisotumab vedotin, which again does not have a biomarker. Why? Because tissue factor is ubiquitously expressed. We alluded to the fact that there may be an opportunity with HER2 IHC [immunohistochemistry]. So, in my mind it is complex and really it’s about staying informed with respect to the therapeutic landscape for cervical cancer or referring these patients to be seen by a provider who takes care of a greater volume of [patients with cervical cancer] and is going to be a partner with you in the [treatment] of these patients.
So again, do not worry alone is a piece of advice. It’s collaboration, it’s partnership, it’s education. It’s working with your medical oncology colleagues. It’s working with your GYN oncology colleagues to make sure that at the end of the day, we’re able to offer our patients the most effective treatment strategies to improve their cancer outcomes.
Transcript is AI generated and edited for readability.