Pembrolizumab ( Keytruda ) is a potent, highly selective humanized monoclonal antibody against PD-1 designed to block interaction with PD-L1 and PD-L2 and remove the inhibition of T-cell activation against cancer. PD-L1 was found to be overexpressed in ovarian cancer and can contribute to malignancy.
Researchers have assessed the safety and efficacy of Pembrolizumab in patients with PD-L1+ advanced ovarian cancer.
KEYNOTE-028 is a nonrandomized, multicohort phase Ib trial of Pembrolizumab in patients with PD-L1+ advanced solid tumors. Key eligibility criteria for the ovarian cancer cohort included advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of prior therapy; PD-L1 expression in greater than or equal to 1% of cells in tumor nests or PD-L1+ bands in stroma as determined by a prototype IHC assay at a central laboratory; and ECOG PS 0-1.
Pembrolizumab 10 mg/kg was given every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity.
Primary end points were: safety, tolerability, and preliminary efficacy.
The response was assessed per RECIST v1.1 by investigators every 8 weeks for the first 6 months and every 12 weeks thereafter.
26 patients were enrolled. Mean age was 58.1; 57.7% were white. 84.6% received prior therapies for recurrent / metastatic disease ( 38.5% received gretaer than or equal to 5 therapies ), and 50% received prior adjuvant therapies.
One patient achieved complete response and 2 patients experienced partial response; 6 patients had stable disease.
Of the 3 patients who responded, all remain in response with duration of response greater than or equal to 24 weeks at the time of analysis.
The best overall ( confirmed ) response was 11.5% ( 95% CI, 2.4-30.2 ). 6/26 ( 23.1% ) had evidence of tumor reduction; 3 had a tumor reduction of at least 30%.
All patients experienced greater than or equual to 1 adverse event ( AE ) ( regardless of treatment ); most common were fatigue ( 42.3% ), anemia ( 30.8% ), and decreased appetite ( 30.8% ).
Drug-related adverse effects occurred in 69.2% of patients ( grade greater than or equal to 3, 1/26 patients ).
Currently, 6 patients are on Pembrolizumab treatment.
In conclusion, PD-1 blockade with Pembrolizumab is well tolerated and has antitumor activity in patients with advanced ovarian cancer. ( Xagena )
Varga A et al, J Clin Oncol 33, 2015 (suppl; abstr 5510)