On November 13, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda®) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score [CPS] ≥ 10) as determined by an FDA-approved test. FDA also approved the PD-L1 IHC 22C3 pharmDx as a companion diagnostic for selecting patients with TNBC for pembrolizumab.

FDA Grants Accelerated Approval to Pembrolizumab for Locally Recurrent Unresectable or Metastatic TNBC

Approval was based on a multicenter, double-blind, randomized, placebo-controlled trial (KEYNOTE-355; NCT02819518) in patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting.

Patients were randomized (2:1) to receive pembrolizumab 200 mg on day 1 every three weeks or placebo in combination with different chemotherapy treatments (paclitaxel protein-bound, or paclitaxel, or gemcitabine plus carboplatin) via IV infusion.

The main efficacy outcome measure was progression-free survival (PFS) in the subgroup of patients with CPS ≥ 10 as assessed by blinded independent review according to the response evaluation criteria in solid tumors 1.1. Median PFS was 9.7 months (95% CI = 7.6, 11.3) in the pembrolizumab plus chemotherapy arm and 5.6 months (95% CI = 5.3, 7.5) in the placebo arm (HR 0.65; 95% CI = 0.49, 0.86; one-sided p value = 0.0012).

The most common adverse reactions (≥ 20%) in patients receiving pembrolizumab plus chemotherapy were fatigue, nausea, diarrhea, constipation, vomiting, alopecia, rash, cough, decreased appetite, and headache. The most common laboratory abnormalities (≥ 20%) were anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, elevated alanine aminotransferase and aspartate aminotransferase, hyperglycemia, hypoalbuminemia, increased alkaline phosphatase, hypocalcemia, hyponatremia, hypophosphatemia, and hypokalemia.

The recommended pembrolizumab dose for adult patients with locally recurrent unresectable or metastatic TNBC is 200 mg every three weeks or 400 mg every six weeks administered prior to chemotherapy for up to 24 months or until patients experience disease progression or unacceptable toxicity. When given with pembrolizumab, either protein-bound paclitaxel 100 mg/m2 on days 1, 8, and 15 every 28 days, or paclitaxel 90 mg/m2 on days 1, 8, and 15 every 28 days, or gemcitabine 1,000 mg/m2 plus carboplatin AUC 2 mg/ml per minute on days 1 and 8 every 21 days is administered via IV infusion.

View full prescribing information for pembrolizumab.

The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The application was granted accelerated approval based on PFS. Continued approval for the indication may be contingent on verification and description of clinical benefit in the confirmatory trials. A description of FDA-expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.     

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.