Merck's Keytruda uncorks full data on latest adjuvant win — this time in melanoma — adding bricks to early cancer wall
In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.
Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.
It’s Keytruda’s latest win in what is known as adjuvant/neoadjuvant cancer, making good on Merck’s mission to bring its blockbuster PD-1 inhibitor into patients before their cancer ever advances. The FDA accepted these data for priority review in August.
At a 14.4-month interim check-in, 11.1% of 487 patients dosed with Keytruda had relapsed or died compared with 16.8% of patients on placebo in the randomized test. The Keytruda arm saw fewer “distant recurrences” at 4.7% of patients compared with 7.8% in the placebo arm.
Merck Research Labs CMO and Keytruda czar Roy Baynes had this to say about the results:
We conducted KEYNOTE-716 to explore whether adjuvant Keytruda, an approved adjuvant treatment option across all resected stage III melanoma, could prolong recurrence-free survival for patients with resected high-risk stage II disease. These findings of a significant 35% reduction in the risk of disease recurrence or death compared to placebo support earlier intervention with Keytruda. We are pleased that these findings have been accepted for priority review by the FDA, and we are grateful to the investigators and patients for their involvement in this important study.
Early cancer has emerged as a key battlefield for the biggest I/O players, with drugs such as Keytruda and Bristol Myers Squibb’s Opdivo settling in as standards of care across advanced cancer and squabbling over relatively minor indications. But adjuvant/neoadjuvant cancer — and the potential to prove immune checkpoint inhibitors can be curative options — has driven those two biggest players into a heated contest for patients, with big revenues on the line.
Merck toplined data from the 716 study back in August, just days after the megablockbuster earned the FDA’s approval to head into early breast cancer patients. The agency gave its rubber stamp to a regimen of Keytruda plus chemo as a neoadjuvant combo followed by adjuvant Keytruda monotherapy in patients with high-risk triple-negative breast cancer.
The data underscoring that approval were particularly contentious: FDA handed Merck a complete response letter on the results, citing a lack of mature safety data and questions over the pivotal study’s pathologic complete response endpoint. But Merck within weeks rolled out OS data showing a win on more mature survival data, and causing the FDA to reverse its earlier decision.
In early June, Merck rolled out data from the KEYNOTE-564 study for Keytruda in adjuvant kidney cancer, with the drug cutting the risk of cancer relapse or death by 32% after a little more than two years compared with placebo in renal cell carcinoma patients with a mid-to-high risk of recurrence after a kidney removal, or after removal of a kidney and metastatic lesions.
Meanwhile, Opdivo sports an adjuvant approval of its own from May in resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy. The approval was based on results from the Phase III CHECKMATE-577 study, which found a statistically significant improvement in disease-free survival (DFS) over placebo, which was defined as the time between randomization and the first recurrence date, or death, from any cause.
A month before, the FDA granted priority review to Opdivo as an adjuvant treatment in muscle-invasive urothelial cancer.