CheckMate 358 is an ongoing phase I/II study which enrolled patients with different types of virus-associated tumours. I have reported the results of the gynaecological cohort, so patients with recurrent or metastatic cervical, vaginal and vulva carcinoma, have been treated in this trial. In the gynaecological cohort 24 patients have been treated, those patients had, for the majority of them, cervical cancer – 19 patients of them had cervical cancer and 5 patients had vaginal or vulva carcinoma. Among those 24 patients the objective response rate was 20% and the disease control rate was 70%. The median duration of response was not reached in this trial but the median follow-up was 31 weeks for the patients.
And those cancers were definitely associated with, for example, HPV status?
Yes. In our cohort, among the 24 patients 14 of them have been tested for HPV and among those 14 patients all of them were HPV positive. HPV has been tested locally, so we have reported the results of HPV determined locally.
I was looking through the results there and it seemed that as well as the overall response rate of 20% the adverse event came in at about 70%. That is quite significant.
In our cohort there were only three patients who had grade 3 or 4 treatment related adverse events which represents 12% of the population. So that’s not a lot and usually it’s less than what we usually see with chemotherapy. Among all the cohort we have observed some side effects that were manageable for the majority of them and that were consistent with previous toxicity observed with nivolumab monotherapy.
There does seem to be a class associated risk of side effects being either as common as a partial response or it might also be that I’ve heard people say that those who have this severe grade 3, grade 4 response are also the ones who are responding most to the therapy.
In this cohort for instance we didn’t make the correlation between the patients who had toxicity, the most severe toxicity, and the response. But yes, it has been observed in other cohorts that patients that experience sometimes the most severe adverse events have a better response but in our cohort it’s just impossible to say.
You said this was a phase I study, are there plans for a phase II dose escalation?
For the moment what is planned for the next steps in this study, the next step is to combine nivolumab plus ipilimumab, an anti-CTLA4, to increase the objective response rate and to increase the efficacy. So that’s the plan for the moment.
Is there anything else you’d like to add, any further thoughts?
The main conclusion of our trial is to say that we observed some encouraging signs of activity with nivolumab monotherapy among patients with recurrent or metastatic cervical, vaginal and vulva cancers. The objective response rate was encouraging – 20% response rate and 70% disease control rate. That’s quite nice results. The important thing as well is that all the objective responses were durable in our trial and lasted for at least six months. At the time of the cut-off all our patients with a partial response were still ongoing and there were still 9 patients out of 24 that were still free from progression.