Merck's Keytruda Stakes Its Claim To First-Line Use In Advanced Cervical Cancer
Top-Line KEYNOTE-826 Results
Executive Summary
Combining Merck & Co’s pembrolizumab with chemotherapy first-line improves survival and PFS in metastatic cervical cancer, reinforcing its position in a condition in the sights of a number of other companies, although usually in later lines of therapy.
Top-line data from the pivotal KEYNOTE-826 trial show Merck & Co., Inc.’s checkpoint inhibitor Keytruda (pembrolizumab) improves overall survival and progression free survival when used as part of first-line therapy for metastatic cervical cancer, supporting the move of the checkpoint inhibitor to earlier lines of therapy in the condition.
There is an unmet need for drugs to treat metastatic cervical cancer, which often affects young and middle-aged women. “KEYNOTE-826 is the first study to show positive results for immunotherapy in first-line persistent, recurrent or metastatic cervical cancer,” Merck noted. The positive outcome was seen regardless of the PD-L1 status of the patients.
The big pharma also noted that the effects of Keytruda on overall survival (OS) and progression-free survival (PFS) in 617 patients with persistent, recurrent or metastatic cervical cancer were “significant and clinically meaningful,” and said further details of KEYNOTE-826 would be shared at a future congress, and discussed with regulatory authorities.
Keytruda is already approved in the US for the second-line treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (with a combined positive score (CPS) equal to or greater than 1), as determined by an FDA-approved test. US regulators granted Keytruda an accelerated approval in this indication, and KEYNOTE-826 is also acting as the confirmatory trial for that decision, Merck noted.
The interim results of the study come just over a month after Sanofi/Regeneron Pharmaceuticals, Inc.’s Libtayo (cemiplimab), reported improved OS and PFS survival in advanced cervical cancer patients who had previously progressed on chemotherapy. (Also see "Cervical Cancer Data Inject Fresh Life Into Sanofi's Libtayo" - Scrip, 13 May, 2021.)
Other drugs are also in late-stage development for cervical cancer, according to Informa’s Biomedtracker database, include Agenus Inc.’s anti-PD-1 antibody balstilimab, a BLA submission for which was accepted in June for recurrent or metastatic cervical cancer in patients with disease progression on or after chemotherapy. (Also see "PD-1 Inhibitor Market Poised For A New Round Of Expansion: After GSK’s Jemperli Approval, US FDA Still Has Three Novel Candidates Under Review" - Pink Sheet, 23 Apr, 2021.)
Another is Seagen Inc. /Genmab A/S’s antibody-drug conjugate, tisotumab vedotin, which is expected to be launched later this year for second-line metastatic cervical cancer treatment; the US FDA action date is 10 October 2021, for a priority review (see sidebar).
There are just over 4,000 deaths in the US annually, and more than 300,000 worldwide, from cervical cancer.
KEYNOTE-826 involved the use of Keytruda in combination with platinum-based chemotherapy (paclitaxel/cisplatin or paclitaxel/carboplatin) with or without bevacizumab, compared with platinum-based chemotherapy with or without bevacizumab. Patients had not previously been treated with systemic chemotherapy and were no longer amenable to curative treatment, such as surgery and or radiotherapy.