Regulatory Decision Summary for Keytruda (pembrolizumab)

This Supplemental New Drug Submission (SNDS) was submitted to expand the use of Keytruda (pembrolizumab) to include a new indication for the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. In addition, this submission was part of the United States Food and Drug Administration (FDA’s) Project Orbis.

After evaluation of the submitted data package, Health Canada authorized Keytruda for the following indication:

Keytruda, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or GEJ adenocarcinoma.

Keytruda currently has various monotherapy and combination indications to treat many types of cancers (e.g. melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, triple negative breast cancer, head and neck squamous cell carcinoma, cervical cancer) at various disease stages (e.g. adjuvant, neoadjuvant, metastatic disease).

Authorization was based on the safety and efficacy results from a Phase III, global, multi-centre, randomized, double-blind, placebo-controlled clinical trial, KEYNOTE-859. This study enrolled 1,579 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma who were naïve to treatment. These patients received either Keytruda (200 mg) or placebo in combination with one of two investigator’s choice chemotherapy regimens: either 5-fluorouracil (800 mg/m²/day for 5 days) and cisplatin (80 mg/m² for up to 6 cycles) (FP regimen) or capecitabine (1,000 mg/m² twice a day for 14 days) and oxaliplatin (130 mg/m² up to 6-8 cycles) (CAPOX regimen).

The primary efficacy endpoint was overall survival (OS) ) in the all randomized population. Additional efficacy measures include progression-free survival (PFS) and objective response rate (ORR). At the pre-specified interim analysis, OS was statistically and clinically significant as patients in the Keytruda arm had a median survival of 12.9 months compared to those in the placebo arm with 11.5 months. It was also noted that a positive association was observed between PD-L1 combined positive score (CPS) and the magnitude of treatment benefit. Generally speaking, patients whose tumours had a higher CPS demonstrated a longer survival benefit.

The most common adverse reactions reported (≥20% incidence) were: diarrhea, colitis, vomiting, and nausea. These safety findings were consistent with previous observations. In this Phase III trial, elderly patients had higher rates of treatment-related Grade 3+ adverse and serious adverse reactions. This information has been included in the Product Monograph for the benefit of patients and health professionals.

The recommended dose of Keytruda is 200 mg administered as an intravenous infusion every 3 weeks up to 24 months (or 35 doses). View the Keytruda Product Monograph for details.

An updated Risk Management Plan (RMP) for Keytruda was reviewed by Health Canada and considered acceptable.

For further details about Keytruda please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.