Keytruda Monotherapy Fails in Phase 3 TNBC Trial

May 20, 2019

Impact Level: Moderate

• Merck has announced that its Phase 3 KEYNOTE-119 trial assessing Keytruda (pembrolizumab) monotherapy compared to chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) in 2L and 3L metastatic triple-negative breast cancer (TNBC) patients did not meet the primary endpoint of OS.
• In accordance with the study protocol, other endpoints (PFS, ORR, disease control rate, and duration of response) were not formally tested since OS was not met.
• Merck plans to present these results at an upcoming medical conference.

inThought Analysis

The failure of KEYNOTE-119 marks a rare setback for Keytruda.

TNBC is a typically aggressive subtype of breast cancer that accounts for approximately 15% of all cases. Current treatment options are considered suboptimal, although Roche won FDA accelerated approval for the use of Tecentriq in combination with Abraxane in PD-L1+ TNBC in March 2019.

TNBC has been a challenging breast cancer subtype and perhaps the addition of chemotherapy to a PD-1/PD-L1 inhibitor is required. It is also worth noting that Tecentriq/Abraxane was approved based on PFS data (a co-primary endpoint, along with OS, in the pivotal IMpassion130 study). OS data are still maturing, but an interim look at the ITT population did not show a statistically significant benefit over Abraxane monotherapy. A “clinically meaningful” OS improvement in the PD-L1-positive population was noted (25.0 vs 15.5 months, HR=0.62). In addition, Roche elected to focus on patients with PD-L1-positive tumors and it could be that Merck is now wishing it had done the same.

The -119 trial represented the only potential near-term PD-1 axis inhibitor competition for Tecentriq, although Keytruda is being studied in other Phase 3 TNBC trials, including the 1L KEYNOTE-355 trial, which compares Keytruda/chemotherapy to chemotherapy and may produce topline data towards the end of 2019.

Source: Merck press release