The FDA grants KEYTRUDA® (pembrolizumab) accelerated approval for the treatment of R/R cHL

On the 14^th March 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to KEYTRUDA® (pembrolizumab) for the treatment of pediatric and adult patients with classical Hodgkin Lymphoma (cHL) who are refractory or who have relapsed after ≥ 3 prior lines of treatment.¹

This accelerated approval for pembrolizumab, a monoclonal anti-PD-1 IgG4 antibody, is based on the phase 2 KEYNOTE-087 (NCT02453594) trial, which investigated pembrolizumab treatment in patients with R/R cHL.

Key Highlights of KEYNOTE-087:¹

• Pts enrolled = 210; Median age = 35yrs (range, 18–76yrs); Median follow-up = 9.4 months
• Pembrolizumab administered at 200mg every 3 weeks in until PD, unacceptable toxicity, or up to 2yrs in pts who did not experience progression
• ORR = 69% (95% CI, 62–75%); CR = 22%; PR = 47%
• Median DoR in responding pts (n=145) = 11.1 months (range, 0+ to 11.1)
• Most frequent AEs = fatigue (26%), pyrexia and cough (24% each), musculoskeletal pain (21%), and diarrhea and rash (20% each)
• SAEs reported in 16% pts; the most common SAEs incl. pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster
• AEs leading to discontinuations in 5% pts; AEs leading to treatment interruptions in 26% pts
• Two deaths reported, both unrelated to disease: septic shock (n=1) and GvHD after subsequent allo-HSCT (n=1)

For safety data, 40 pediatric patients with PD-L1-positive, advanced, R/R solid tumors, advanced melanoma, or lymphoma were assessed by the FDA. The safety profile was consistent with that reported in adults. Some AEs were observed at a higher rate (≥15% difference) in pediatric patients, such as fatigue, vomiting, abdominal pain, hypertransaminasemia, and hyponatremia.

The approved regimens of pembrolizumab are 200mg every 3 weeks for adults and 2mg/kg (up to 200mg) every 3 weeks for pediatric patients. This is the first FDA indication for pembrolizumab in a hematologic malignancy.

To date, pembrolizumab has FDA approvals in:²

• Patients with unresectable or metastatic melanoma
• Patients with metastatic NSCLC whose tumors have high PD-L1 expression [(Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC
• Patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy
  • Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA®
• Patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy
  • This indication is approved under accelerated approval based on tumor response rate and durability of response