Alternative pembrolizumab dosing schedule safe, effective in metastatic melanoma
An alternative pembrolizumab dosing regimen of 400 mg every 6 weeks appeared safe and effective for patients with metastatic melanoma, according to first clinical outcomes data from KEYNOTE-555 cohort B presented at the virtual American Association for Cancer Research Annual Meeting.
“Pembrolizumab [Keytruda, Merck] is approved globally in multiple cancer indications at a dose of 200 mg or 2 mg/kg every 3 weeks,” Mallika Lala, PhD, associate principal scientist at Merck & Co., said during a presentation. “An alternative dosing regimen of 400 mg every 6 weeks is proposed as an additional option to the currently approved dose, which provides convenience and flexibility to patients and providers — the need for which is particularly exemplified by the current COVID-19 pandemic. We selected this alternative dose based upon pharmacokinetic and exposure-response modeling and simulation data that formed the basis of its approval in markets including the European Union, Australia and New Zealand.”
The open-label KEYNOTE-555 cohort B study was designed to evaluate the alternative dosing schedule among 100 patients (mean age, 64 years; 59.1% men; mean body weight, 85 kg) with metastatic melanoma. Investigators sought to validate model-based assessments, as well as determine efficacy and safety of the 6-week regimen compared with historical data.
Researchers acquired observed pharmacokinetic data over the first treatment cycle for 44 patients. They compared these data with predictions from a model based upon 2,993 patients with various tumor types included in five clinical trials.
Results showed the geometric mean for trough concentration at 6 weeks was 14.5 ug/mL with the alternative 400 mg 6-week dosing schedule compared with 18.1 ug/mL with 200 mg pembrolizumab every 3 weeks (18% lower) and 13.4 ug/mL with 2 mg/kg every 3 weeks (11% higher).
Moreover, the geometric mean of observed peak concentration at the end of infusion with the alternative 6-week dosing was 136 ug/mL, which was 38% lower than the geometric mean of 220 ug/mL with 10 mg/kg pembrolizumab every 2 weeks, the highest clinically tested dose.
Overall response rate was 38.6% (95%CI, 24.4-54.5) with the 6-week dosing regimen and 35.1% (95% CI, 32.5-37.9) with the 3-week dosing regimen based on historical trials. Nearly 60% of patients experienced a more than 30% reduction in target lesion size.
In addition, the safety of the 6-week regimen appeared comparable to that observed in more than 12 tumor types.
“These data from KEYNOTE-555 cohort B support that pembrolizumab administered at 400 mg every 6 weeks is a safe and effective dosing regimen and offers a more convenient option for patients and physicians to meet individual needs and preference,” Lala said. “We selected the 6-week regimen because it achieved an optimal balance between what was scientifically sound based upon pharmacokinetic modeling, as well as it provides an extended dosing frequency that offers sufficient convenience in clinical practice. PFS data are currently immature, but we will disclose this data once available.” – by Jennifer Southall
Lala M, et al. Abstract CT042. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).
Disclosures: Lala reports employment with Merck & Co. Please see the abstract for all other researchers’ relevant financial disclosures.
It is very good to see that this higher dose can decrease the number of visits patients have to make to outpatient facilities and further open the possibility of home care for these patients. he pharmacokinetic are consistent across the different tumor types very encouraging. This also means that in the adjuvant setting the frequency of hospital will decrease in the near future and this is a great service to our patients. We now await the next step in ease of administration and potential self-administration with cutaneous development of pembrolizumab. This study is extremely encouraging, and it is wonderful to see that it is consistent with all datasets published thus far.