Abstract CT042: Pembrolizumab 400 mg Q6W dosing: First clinical outcomes data from Keynote-555 cohort B in metastatic melanoma patients
Authors: Mallika Lala, Omobolaji Akala, Elliot Chartash, Mizuho Kalabis, Shu-Chih Su, Dinesh de Alwis, Vikram Sinha, Lokesh Jain
Journal: Cancer Research (2020)

Abstract Background: Pembrolizumab is approved globally in multiple cancer indications at a dose of 200 mg or 2 mg/kg every three weeks (Q3W). An alternative dosing regimen of 400 mg every six weeks (Q6W), which provides convenience and flexibility to patients and prescribers, is also approved in markets including the European Union (EU), Australia and New Zealand based on pharmacokinetic (PK) modeling and simulation. KEYNOTE-555 Cohort B is an open-label, clinical study in patients with metastatic melanoma designed evaluate the Q6W dosing. The preliminary PK data to validate the model-based assessments as well as efficacy and safety of the Q6W regimen compared to historical data will be described. Methods: A total of 101 patients are enrolled in this study; complete cycle 1 PK data from 37 patients are available. Observed concentration-time profiles from cycle 1 were compared with predictions from the model, which is based on 2993 patients from 5 clinical trials across tumor types. The associated efficacy and safety from these patients will be reviewed and compared to previous clinical trials in advanced melanoma. Results: The demographics from KN-555 Cohort B were similar to previous trials of pembrolizumab in metastatic melanoma, with mean age: 62 years, mean body weight: 85 kg, and 34% female patients. The observed concentrations for 400 mg Q6W were well within the 90% prediction intervals of simulated concentrations using the model. The geometric mean (GM) of observed trough concentration at six weeks (Ctrough) at 400 mg Q6W is 14.5 ug/mL, which is 18% lower than at 200 mg Q3W (18.1 ug/mL) and 11% higher than at 2 mg/kg Q3W (13.4 ug/mL). The GM of observed peak concentration at the end of infusion at 400 mg Q6W is 136 ug/mL, which is below (38% lower) that at the highest clinically tested dose of 10 mg/kg Q2W (220 ug/mL). The ORR in KN-555 Cohort B is comparable to the ORR in previous pembrolizumab studies in metastatic melanoma, indicating similarity of efficacy between the Q6W and Q3W regimens. The safety of the Q6W regimen is comparable to the extensive pembrolizumab safety profile that has been demonstrated in over twelve tumor types. Conclusion: The preliminary PK, efficacy and safety analyzed from KN-555 Cohort B validates the findings from the model-based assessment, of a consistent benefit-risk profile for a 400 mg Q6W regimen as compared to the 200 mg (or 2 mg/kg) Q3W regimen. The study supports that pembrolizumab Q6W is a safe and effective dosing regimen and offers a more convenient option for patients and physicians. Citation Format: Mallika Lala, Omobolaji Akala, Elliot Chartash, Mizuho Kalabis, Shu-Chih Su, Dinesh de Alwis, Vikram Sinha, Lokesh Jain. Pembrolizumab 400 mg Q6W dosing: First clinical outcomes data from Keynote-555 cohort B in metastatic melanoma patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT042.