Mallika Lala, Ph.D.
Mallika is currently positioned as Associate Principal Scientist at Merck & Co., Inc. in the Quantitative Pharmacology and Pharmacometrics group. She has ~10 years of drug development experience across therapeutic modalities, including early and late clinical oncology. Most recently, she has been involved with the clinical development of pembrolizumab across indications and regulatory submissions in several global markets. Before joining Merck, Mallika worked at the US FDA, where she was primarily focused on application of innovative quantitative approaches to enhance pediatric drug development. She also has previous experience in the pharmaceutical industry in India where she was involved with Phase 1 clinical trials and providing training in quantitative science techniques. Mallika obtained a Ph.D. in pharmaceutical sciences from Virginia Commonwealth University in 2011.
What challenges have oncologists faced in terms of treatment scheduling during the COVID-19 pandemic?
In light of the COVID-19 pandemic, the oncology community has had to rapidly adapt its approach to cancer care in order to minimize the amount of time patients with cancer spend receiving treatment in clinics and hospitals, where they are at greater risk of infection.
What was the rationale for the 6-weekly dosage schedule of pembrolizumab?
We are driven by a passion to deliver meaningful advances for patients facing cancer and this includes identifying ways to ensure that patients have options that meet their needs and can reduce the amount of time they spend receiving treatment. Patients diagnosed with difficult-to-treat cancers face a number of complexities associated with their treatment, including frequent infusions and a significant amount of time devoted to care. Having two dosing options for KEYTRUDA would provide additional flexibility in determining a treatment program that works best for patients based on individual needs.
While we pursued Q6W dosing for KEYTRUDA prior to the COVID-19 pandemic, now, new treatment options that will reduce the amount of time patients spend receiving treatment are increasingly important.
Could you tell us a little about the aims and design of the KEYNOTE-555 study?
KEYNOTE-555 Cohort B is an ongoing single arm, open-label study in treatment-naïve metastatic melanoma, evaluating pembrolizumab monotherapy at a dose of 400 mg Q6W in 100 patients receiving treatment for up to 2 years. The primary endpoint is objective response rate (ORR); secondary endpoints include pharmacokinetic (PK) exposures, progression-free survival (PFS) and safety.
What were the efficacy and safety findings from cohort B of this study?
Interim data from Cohort B of KEYNOTE-555 demonstrated that the KEYTRUDA 400 mg every six-week dosing regimen has comparable efficacy and safety as the KEYTRUDA 200 mg every three-week regimen. The objective response rate (ORR) was 38.6% (n=17/44) (95% CI, 24.4-54.5) for patients treated with KEYTRUDA 400 mg Q6W. Pharmacokinetic (PK) exposures with the KEYTRUDA Q6W regimen were within clinical experience with other tested dosing regimens i.e. 2 mg/kg Q3-wks, 200 mg Q3-wks and 10 mg/kg Q2-wks. The safety profile of the KEYTRUDA Q6W regimen was consistent with the safety profile of the approved KEYTRUDA Q3W dosing regimen, which has been demonstrated in more than 12 tumor types (KEYTRUDA Package Insert). These findings are particularly meaningful against the current backdrop of the COVID-19 pandemic, as less frequent dosing ultimately reduces patient exposure to clinics and hospitals, where they are at greater risk of getting infections.
For which applications has FDA approval of 6-weekly dosing been given?
The US Food and Drug Administration (FDA) has approved an additional recommended dosage of 400 mg every six weeks for KEYTRUDA across all adult indications, including monotherapy and combination therapy. A full list of approved KEYTRUDA indications can be found in the approval news release (see “Selected KEYTRUDA Indication”) here.
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Published: 13 May 2020