Merck & Co/MSD has chalked up a clinical trial win for its PD-1 inhibitor Keytruda in triple-negative breast cancer that it says may form the basis of regulatory filings.
An interim analysis of the KEYNOTE-355 trial showed that adding Keytruda (pembrolizumab) to chemotherapy in previously-untreated TNBC patients whose tumours test positive for the PD-L1 biomarker extended the time to disease progression or death compared to chemo plus placebo.
Keytruda is the top-selling PD-1/PD-L1 inhibitor worldwide thanks to its dominance in lung cancer, but in TNBC it is playing catch-up with Roche’s Tecentriq (atezolizumab).
Roche’s drug was approved in the US and Europe for use in adults with PD-L1-positive unresectable, locally advanced or metastatic TNBC last year, and the company estimates the indication could be worth up to $1bn in additional revenues for the drug.
TNBC is an aggressive and hard-to-treat subtype of breast cancer, representing around 15% of all breast cancer worldwide, approximately 300,000 cases every year. Patients who are PD-L1 positive represent a subgroup of about 40% of this total.
The actual progression-free survival (PFS) numbers for KEYNOTE-355 – which compared Keytruda plus Bristol-Myers Squibb/Celgene’s Abraxane (nab-paclitaxel), paclitaxel or gemcitabine/carboplatin to the chemo drugs given alone – aren’t being revealed yet but will be presented at a future medical conference and shared with regulators.
The positive top-line results are a relief to Merck, which suffered a setback in its TNBC programme last year when Keytruda failed to show an improvement over chemotherapy in patient survival when given as a monotherapy in the phase 3 KEYNOTE-119 trial.
The design of KEYNOTE-355 is similar to that of Roche’s IMpassion130 study of Tecentriq plus chemo in TNBC, so the two drugs will compete toe-to-toe if Keytruda gets approval – assuming the results are similar.
Oncologists have said there is still debate about what the best chemotherapy backbone is for anti-PD-L1 treatment of TNBC, and that could leave room for rivals to challenge Tecentriq plus Abraxane.
Meanwhile, Merck is also carrying out two additional studies of Keytruda to try to expand its clinical profile in TNBC.
KEYNOTE-522 involves patients with early-stage TNBC and is comparing Keytruda chemotherapy given before and after surgery (neoadjuvant/adjuvant therapy) to try to prevent recurrence of the disease. Preliminary neoadjuvant results showed an improvement for Merck’s drug in response rate, but final results aren’t due until 2025.
KEYNOTE-242 is a National Cancer Institute (NCI) sponsored trial testing adjuvant use of the checkpoint inhibitor after neoadjuvant chemotherapy due to generate results in 2026.