On the 23rd March 2017, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) gave a ‘positive opinion’ to KEYTRUDA® (pembrolizumab), a monoclonal anti-PD-1 IgG4 antibody, for the treatment of adult patients with classical Hodgkin Lymphoma (cHL) who have failed Autologous Stem Cell Transplantation (ASCT) and brentuximab vedotin, or who are transplant-ineligible and have failed brentuximab vedotin.
The granting of a ‘positive opinion’ follows the accelerated approval for KEYTRUDA® (pembrolizumab) by the U.S. Food and Drug Administration (FDA) on the 14th March 2017 in both adult and pediatric patients. The FDA’s accelerated approval for pembrolizumab was based on the phase II KEYNOTE-087 (NCT02453594) trial, which investigated pembrolizumab treatment in patients with R/R cHL.
Key Highlights of KEYNOTE-087:
- 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 ASCT (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 already fully approved regimens of pembrolizumab are 200mg every 3 weeks for adults and 2mg/kg (up to 200mg) every 3 weeks for pediatric patients, according to the product prescribing information page.
The full EMA CHMP positive opinion is as follows:
“Keytruda as monotherapy is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV.”
- EMA CHMP Summary of opinion: Keytruda (pembrolizumab). 2017 Mar 23. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion/human/003820/WC500224298.pdf. [Accessed 2017 Mar 28]
- FDA Approves Pembrolizumab for Hodgkin Lymphoma. 2017 Mar 14. http://www.onclive.com/web-exclusives/fda-approves-pembrolizumab-for-hodgkin-lymphoma. [Accessed 2017 Mar 15].
- KEYTRUDA® Prescribing Information. 2017 Mar. http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. [Accessed 2017 Mar 28].