The FINANCIAL — Merck, known as MSD outside the United States and Canada, on June 5 announced findings from three separate studies evaluating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in combination with other treatment regimens including talimogene laherparepvec, dabrafenib plus trametinib, or low-dose ipilimumab in patients with advanced melanoma.
These data, from MASTERKEY-265, KEYNOTE-022, and KEYNOTE-029, respectively, are included in the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstracts #9568, #3014, and #9506).
“We continue to build on our leadership in advanced melanoma by evaluating KEYTRUDA with multiple combination partners utilizing diverse mechanisms of action with the goal of improving outcomes while maintaining tolerability,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “These encouraging early data point to the potential for KEYTRUDA to become an important component of combination therapy in melanoma.”
Each of these studies was designed to answer specific questions around the use of KEYTRUDA in various combination treatment settings. In each of the three studies, the safety profile of the combination regimens was shown to be manageable, according to Merck.
“Anti-PD-1 drug therapies, like pembrolizumab, have shown benefit as a monotherapy in the treatment of advanced melanoma, and it is important to understand their potential in combination with other effective therapeutics, including immunotherapies and targeted therapies,” said Dr. Georgina Long, professor of melanoma medical oncology and translational melanoma research, Melanoma Institute Australia and University of Sydney. “Physicians are focused on different treatment paths for different types of patients and, with the promising data presented at ASCO this year, we aim to better understand the role of monotherapy and develop combination treatment strategies for patients with advanced melanoma who may not benefit as much from monotherapy.”
The KEYTRUDA (pembrolizumab) clinical development program includes patients with more than 30 tumor types in more than 270 ongoing or planned studies, including more than 100 trials that combine KEYTRUDA with other cancer treatments – these include other immuno-oncology therapies, standard therapies and targeted therapies.
Findings from MASTERYKEY-265: KEYTRUDA with talimogene laherparepvec (Abstract #9568)
MASTERKEY-265 is an ongoing phase 1b study evaluating the safety, efficacy, and tolerability of KEYTRUDA in combination with talimogene laherparepvec in patients with previously untreated, unresectable advanced melanoma. The trial is a collaboration between Merck and Amgen. Talimogene laherparepvec is a herpes simplex virus-1 (HSV-1)-based oncolytic immunotherapy used for the treatment of melanoma lesions in the skin and lymph nodes.
Updated data from 21 evaluable patients showed that a combination of KEYTRUDA (200 mg every two weeks) with talimogene laherparepvec (up to 4 mL of 106 PFU/mL, then 108 PFU/mL every two weeks) resulted in a confirmed overall response rate (ORR) of 57.1 percent (n=12/21) (95% CI, 34-78.2), per modified immune-related response criteria (irRC) – 23.8 percent were complete responses (n=5/21) and 33.3 percent were partial responses (n=7/21).
The safety profile of KEYTRUDA in combination with talimogene laherparepvec was consistent with that observed in previously reported studies of KEYTRUDA or talimogene laherparepvec monotherapy in patients with advanced melanoma. Seven patients (33%) experienced treatment-related Grade 3-4 adverse events, including: anemia, aseptic meningitis, autoimmune hepatitis, generalized rash, headache, hyperglycemia, hypoglycemia, hypophosphatemia, increased alanine aminotransferase, increased aspartate aminotransferase, increased gamma-glutamyltransferase, muscle spasms, macular rash, rash, and pneumonitis. Two patients (10%) experienced a treatment-related adverse event that led to permanent discontinuation of KEYTRUDA. No patients (0%) experienced a treatment-related adverse event that led to permanent discontinuation of talimogene laherparepvec. No dose-limiting toxicities were reported.
These data were presented by Dr. Long on June 4.
Findings from KEYNOTE-022: KEYTRUDA with dabrafenib plus trametinib (Abstract #3014)
KEYNOTE-022 is an ongoing phase 1/2 study designed to assess the safety and efficacy of KEYTRUDA in combination with dabrafenib plus trametinib in patients with advanced melanoma. Dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) is a combination regimen used in the treatment of certain types of advanced melanoma.
Based on early data from the 15 patients treated in phase 1, treatment with KEYTRUDA (pembrolizumab) (2 mg/kg every three weeks) with dabrafenib (150 mg twice daily) plus trametinib (2 mg daily) resulted in nine partial responses, five of which were confirmed. Additionally, of the patients with lesion data available, 92.3 percent experienced a reduction in tumor size (n=12/13).
Grade 3-4 adverse events occurring in greater than or equal to 10 percent of patients included ALT increased (n=3), AST increased (n=3), pyrexia (n=3), GGT increased (n=2), and WBC count decreased (n=2). Four patients (26.7%) experienced a treatment-related adverse even that led to discontinuation. There were no treatment-related deaths. The phase 2 part of the study is ongoing and will further evaluate the safety and efficacy of the KEYTRUDA combination regimen compared to dabrafenib plus trametinib.
On June 5, these data will be presented by Dr. Antoni Ribas in a poster session from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 4:45 – 6:00 p.m. CDT (Location: Hall B1).
Findings from KEYNOTE-029: KEYTRUDA with low-dose ipilimumab (Abstract #9506)
KEYNOTE-029 is an ongoing phase 1/2 study evaluating the safety, efficacy, and tolerability of KEYTRUDA in combination with low-dose ipilimumab in patients with advanced melanoma. Ipilimumab is a CTLA-4 inhibitor used in the treatment of melanoma.
Findings from 153 evaluable patients with advanced melanoma showed that KEYTRUDA (2 mg/kg every three weeks) in combination with low-dose ipilimumab (1 mg/kg every three weeks for four doses) demonstrated an ORR of 57 percent (95% CI, 49-65) by independent central review – 10 percent were complete responses (n=15/153) and 47 percent were partial responses (n=72/153). The six-month progression-free survival (PFS) rate was 70 percent and the six-month overall survival (OS) rate was 93 percent. At the time of analysis, median PFS (95% CI, 12.4 months-NR) and OS (95% CI, NR-NR) were not reached; 98 percent of responses were ongoing. Median follow-up duration was 10.0 months (range 0.8-14.1).
Sixty-four patients (42%) experienced treatment-related Grade 3-4 adverse events. Thirty-eight patients (25%) experienced immune-mediated Grade 3-4 adverse events, including: colitis, hepatitis, hyperthyroidism, hypophysitis, infusion reaction, pancreatitis, pneumonitis, nephritis, skin reactions, and type 1 diabetes mellitus. Sixteen patients (10%) experienced a treatment-related adverse event that led to ipilimumab discontinuation only, 11 patients (7%) experienced a treatment-related adverse event that led to KEYTRUDA (pembrolizumab) discontinuation after completion or discontinuation of ipilimumab, and 16 patients (10%) experienced a treatment-related adverse event that led to ipilimumab and KEYTRUDA discontinuation, including one patient who discontinued ipilimumab for colitis and later discontinued KEYTRUDA for increased lipase. There were no treatment-related deaths.
These data will be presented in an oral session by Dr. Long on June 6 at 2:51 p.m. CDT (Location: Arie Crown Theater).
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