Merck announces OS results from pivotal Phase 3 KEYNOTE-A18 trial

Merck announced the first presentation of overall survival results from the pivotal Phase 3 KEYNOTE-A18 trial, also known as ENGOT-cx11/GOG-3047, investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with concurrent chemoradiotherapy for newly diagnosed patients with high-risk locally advanced cervical cancer. At a median follow-up of 29.9 months, KEYTRUDA in combination with concurrent CRT reduced the risk of death by 33% versus concurrent CRT alone for these patients. For patients who received the KEYTRUDA-based regimen, the 36-month OS rate was 82.6% versus 74.8% for those who received concurrent CRT alone. Median OS was not reached in either group. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. KEYNOTE-A18 is one of four Phase 3 studies of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, in addition to KEYNOTE-522 in newly diagnosed, high-risk early-stage triple-negative breast cancer and KEYNOTE-671 in resectable stage II, IIIA or IIIB non-small cell lung cancer, as well as KEYNOTE-564 in renal cell carcinoma for patients at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. These results are being discussed with regulatory authorities worldwide. As previously reported, KEYNOTE-A18 met its other primary endpoint of progression-free survival in 2023. These PFS data were presented at the ESMO Congress 2023 and supported the U.S. Food and Drug Administration’s approval of KEYTRUDA in combination with CRT for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer in January 2024. In the U.S., KEYTRUDA has two additional approved indications in cervical cancer: in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (Combined Positive Score greater than or equal to1) as determined by an FDA-approved test; and as a single agent, for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 as determined by an FDA-approved test. As announced, data spanning more than 20 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2024. KEYNOTE-A18, also known as ENGOT-cx11/GOG-3047, is a randomized, double-blind Phase 3 trial sponsored by Merck and conducted in collaboration with the European Network for Gynaecological Oncology Trial groups and the GOG Foundation investigating KEYTRUDA in combination with CRT compared to placebo plus concurrent CRT for the treatment of newly diagnosed high-risk locally advanced cervical cancer where patients are treated with definitive intent. The primary endpoints are PFS and OS, and secondary endpoints include complete response rate, objective response rate and safety. The trial enrolled 1,060 patients who were randomized 1:1 to receive: KEYTRUDA every three weeks for five cycles concurrent with cisplatin weekly for five cycles radiotherapy, followed by KEYTRUDA every six weeks for 15 cycles; Placebo IV Q3W for five cycles concurrent with cisplatin weekly for five cycles and radiotherapy, followed by placebo IV Q6W for 15 cycles. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade greater than or equal to 3 treatment-related adverse eventsoccurred in 69.1% of patients receiving KEYTRUDA plus concurrent CRT versus 61.3% of patients receiving placebo plus concurrent CRT. No new safety concerns were identified. Immune-mediated adverse events of any grade occurred in 39% of patients receiving the KEYTRUDA regimen and 17% of patients receiving the placebo regimen. Grade 3-5 immune-mediated AEs occurred in 4.7% versus 1.3%, respectively. The most common of these all-grade immune-mediated AEs was hypothyroidism in patients receiving the KEYTRUDA regimen. Immune-mediated AEs led to one death among patients receiving the KEYTRUDA regimen.