Ursula A. Matulonis, MD, on the KEYNOTE-100 Study Design

July 17, 2020

The expert from Dana-Farber Cancer Institute discussed the study design and inclusion criteria for this study of pembrolizumab in patients with advanced recurrent ovarian cancer.

Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, indicated that pembrolizumab monotherapy was associated with modest antitumor activity in patients with recurrent advanced ovarian cancer.

Specifically, there appeared to be a trend toward increased overall response rates with higher PD-L1 expression in both cohorts, as well as durable responses that generally lasted ≥6 months. In addition, no new safety signals were identified in the trial.

In an interview with CancerNetwork®, Ursula A. Matulonis, MD, of the Dana-Farber Cancer Institute, discussed the study design and the criteria for patients to be enrolled in the trial.


So, this is these are the final results of the KEYNOTE-100 trial, and this is an international study that was started a number of years ago, examining the activity of the single agent pembrolizumab, so by itself. And obviously pembrolizumab is an anti-PD-1 checkpoint inhibitor for the treatment of women with advanced and recurrent ovarian cancer. So, the trial design was that patients were divided into 1 of 2 groups. Regardless of group, all patients had recurrent ovarian cancer, they had to have a good performance status of 0 or 1, they had to have also provision of an archival tumor tissue as well. So, for IHC, as well as other future biomarkers that are being done with this trial. The key exclusion criteria: our patients could not have mucinous histology. They could have any other histology, but could not have mucinous histology, no recent bowel obstruction, so no bowel obstruction within 3 months, and then no recent active autoimmune disease, and then no active central nervous system metastasis.

So, patients were enrolled into 2 cohorts, cohort A and then cohort B. Cohort A were less heavily pretreated patients, so they had to have at least 1 per line of treatment, and up to 3 prior lines of treatment. And the platinum-free or treatment-free interval was at least 3 months from the prior treatment and up to 12 months. Most of the patients went on this arm, about 285. And for cohort B fewer patients, these patients in cohort B were more heavily pretreated. So, they had to have between 4 and 6 prior lines of treatment. And they had to have a prior platinum-free or treatment-free interval of at least 3 months. But there is no upper limit cap on the upper limits of the platinum-free or treatment-free interval. And those patients enrolled here were 91 patients. And importantly for the patients who are enrolled into cohort A, they represented, at least the first 100 patients into cohort A, they represented the training set. And these patients led to cutoff points for PD-L1 testing, so examining the CPS score, and basically giving us cutoff points where we would look at specific combined positive scores. Just to remind you, a combined positive score means that it's looking at the number of PD-L1 positive cells. So, it could be a cancer cell, could be a lymphocyte, could be a macrophage, a macrophage divided by the total number of tumor cells, times 100. And the cutoff points for CPS score were 1 or higher or 10 or higher.


Matulonis UA, Shapira R, Santin A, et al. Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer. Presented at: 2020 ASCO Virtual Scientific Program. Abstract #6005.