A trial comparing frontline Keytruda (pembrolizumab) with Yervoy (ipilimumab) for the treatment of advanced melanoma has met its progression-free survival (PFS) and overall survival (OS) endpoints, according to Merck, the company developing Keytruda. The trial will be stopped early, based on a recommendation from an independent data monitoring committee.
In this phase 3 trial, named KEYNOTE-006, Keytruda demonstrated a statistically significant and clinically meaningful improvement in PFS and OS over Yervoy in this patient population. Results will be presented at the upcoming American Association for Clinical Research (AACR) Annual Meeting in April.
Patients enrolled on KEYNOTE-006 had unresectable stage 3 or 4 advanced melanoma and received no more than one prior systemic therapy. The primary endpoints of KEYNOTE-006 were focused on PFS and OS, with secondary endpoints focused on overall response rate (ORR), duration of response and safety.
In KEYNOTE-001, the trial that led to the 2014 approval of Keytruda, ORR (32 percent versus 27 percent) and 12-month OS rates were higher (63 percent versus 58 percent) with the 10-mg/kg dose compared with the 2 mg/kg dose, respectively, though PFS at 24 weeks (37 percent versus 44 percent) and median OS were shorter (18 months versus not reached at data cutoff). The recommended dosing regimen of Keytruda is 2 mg/kg given every three weeks.
In the trial of 173 patients, Keytruda demonstrated an ORR of 24 percent at the recommended dose of 2 mg/kg, with responses lasting 1.4 to 8.5 months. The most common side effects associated with Keytruda (occurring in at least 20 percent of patients) were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia and diarrhea.
Yervoy was approved much earlier, in 2011, for the treatment of patients with unresectable or metastatic disease. The CTLA-4 inhibitor was approved based on a 676-patient study comparing the agent with or without the gp100 vaccine and the vaccine alone. In the trial, patients on either arm receiving Yervoy experienced an OS of approximately 10 months, compared with 6.5 months with the vaccine alone. The most common side effects associated with the agent are fatigue, diarrhea, pruritus, rash and colitis.
Outside of KEYNOTE-006, Keytruda and Yervoy seem headed down different paths.
Yervoy has continued to show long-term benefit and is now moving into later lines of therapy. According to Clinicaltrials.gov, there are 76 open studies looking at the agent in melanoma.
Conversely, Keytruda is being examined in 18 open melanoma studies—further indicating its expansion into other tumor types.
Keytruda has demonstrated activity and acceptable safety in separate phase 1b studies of metastatic triple-negative breast cancer and classical Hodgkin lymphoma. These studies were presented at the 2014 SABCS and ASH meetings, respectively.