Merck says KEYTRUDA demonstrated long-term survival benefit
Merck (MRK) announced long-term efficacy data from the Phase 3 KEYNOTE-006 study and the melanoma cohort of the Phase 1b KEYNOTE-001 study investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with advanced melanoma.
KEYTRUDA is not chemotherapy or radiation therapy—it is an immunotherapy and it works with patient’s immune system to help fight certain cancers. KEYTRUDA can cause immune system to attack normal organs and tissues in any area of your body and can affect the way they work.
A new analysis from KEYNOTE-006 demonstrated durable efficacy benefits among patients who completed two years of KEYTRUDA treatment, combined with updated overall survival results across both studies, confirming anti-tumor activity in advanced melanoma patients.
At a median follow-up of 20.3 months after completion of KEYTRUDA in KEYNOTE-006, 86 percent of patients remained progression-free, the co-primary endpoint for the study.
For the primary endpoint of OS in KEYNOTE-006, the four-year OS rate was 41.7 percent in the pooled KEYTRUDA arms vs. 34.1 percent in the ipilimumab arm; in treatment-naive patients, OS rates were 44.3 percent in the pooled KEYTRUDA arms and 36.4 percent in the ipilimumab arm.
In KEYNOTE-001, the five-year OS rate, a secondary endpoint for the study, was 34 percent in all patients and 41 percent in treatment-naive patients.
The safety profile of KEYTRUDA in both studies was consistent with what has been seen in previous trials among patients with advanced melanoma.
KEYNOTE-006 is a global, open-label, randomized, pivotal, Phase 3 study evaluating KEYTRUDA compared to ipilimumab in patients with unresectable stage III or IV melanoma who had either not been treated previously or who had received a prior targeted therapy for BRAF-mutation positive melanoma/ The study randomized 834 patients to receive KEYTRUDA 10 mg/kg every three weeks, KEYTRUDA 10 mg/kg every two weeks, or four cycles of ipilimumab 3 mg/kg every three weeks.
Treatment continued until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months.
Upon disease progression, eligible patients could receive an additional one year of KEYTRUDA. The co-primary endpoints were progression-free survival and OS; secondary endpoints were overall response rate, duration of response and safety, with an exploratory analysis for health-related quality of life.
With a median follow-up of 45.9 months, the four-year OS rate was 41.7 percent in the pooled KEYTRUDA arms and 34.1 percent in the ipilimumab arm; investigator-reported ORR was 42 percent and 17 percent, respectively.
Median DOR was not reached for KEYTRUDA or ipilimumab; 62 percent of patients in the KEYTRUDA arms and 59 percent of patients in the ipilimumab arm had a response lasting greater than or equal to 42 months.
In treatment-naive patients, the four-year OS rates were 44.3 percent in the pooled KEYTRUDA arms and 36.4 percent in the ipilimumab arm; ORR was 47 percent and 17 percent, respectively.
Median DOR was not reached for KEYTRUDA or ipilimumab; 65 percent of patients in the KEYTRUDA arms and 68 percent of patients in the ipilimumab arm had a response lasting greater than or equal to 42 months. Per study protocol, 18.5 percent of patients completed two years of KEYTRUDA.
With a median follow-up of 20.3 months 86 percent of patients remained progression-free. Eight patients received second-course KEYTRUDA; three discontinued treatment. Among the eight patients, there was one complete response and three partial responses; three patients had stable disease, while the remaining patient had progressive disease.
KEYNOTE-001 is a Phase 1b multicenter, open-label, multi-cohort trial evaluating KEYTRUDA in various advanced cancers, including 655 patients with advanced melanoma. Patients in the melanoma cohorts received 2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks or 10 mg/kg of KEYTRUDA every two weeks until unacceptable toxicity or disease progression.
The primary endpoint was confirmed ORR. The secondary endpoints included PFS, OS and DOR. After median follow-up of 55 months, 35 patients remained on KEYTRUDA therapy.
The investigator-reported ORR, the primary endpoint for KEYNOTE-001, was 41 percent in all patients and 52 percent in treatment-naive patients.
The estimated five-year OS rate was 34 percent in all patients and 41 percent in treatment naive patients. Median OS was 23.8 months in all patients and 38.6 months in treatment-naive patients. Median PFS was 8.3 months and 16.9 months in all patients and treatment-naive patients, respectively. Median DOR was not reached in all responders and in treatment-naive patients; 73 percent of all responses and 82 percent of treatment-naive responses were ongoing at data cut-off.
The longest response observed in all patients was ongoing at 66 months.
The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced melanoma. Treatment-related adverse events occurred in 86 percent of patients including 17 percent with grade 3-4 and eight percent who discontinued.
Twelve percent of patients experienced a serious TRAE including five percent who discontinued treatment. Immune-mediated adverse events and infusion reactions were reported in 23 percent of patients.
Most cases of immune-related adverse events, including hypothyroidism and pneumonitis, were grade 1 or 2. Hypothyroidism was the most commonly reported immune-mediated adverse event, followed by pneumonitis, colitis and skin disorders.
MRK closed at $60.56. It last traded at $61.65.
To read timely stories similar to this, along with money making trade ideas, sign up for a membership to Stockwinners.
This article does not constitute investment advice. Each reader is encouraged to consult with his or her individual financial professional and any action a reader takes as a result of information presented here is his or her own responsibility.