Merck's Keytruda has more data in early triple-negative breast cancer. Will the FDA reverse its prior rejection?

Merck hopes that new data showing Keytruda could prevent disease returning in patients with high-risk early-stage triple-breast cancer could persuade the FDA in reversing a previous complete response letter. (Merck)

In March, the FDA handed Merck & Co. a resounding rejection for Keytruda in high-risk early-stage triple-negative breast cancer and blasted the company for jumping the gun with immature data. Now, the New Jersey pharma believes it has the updated trial results that could persuade the agency.

In patients with high-risk early TNBC, adding Keytruda to chemotherapy before surgery—followed by continuing treatment with Keytruda after surgery—extended the time they lived without disease returning, Merck said Thursday.

The improvement on the so-called event-free survival marker from the phase 3 Keynote-522 trial was both statistically significant and clinically meaningful, the company said, though it didn't share the exact numbers.

The FDA previously rejected Keytruda’s application in that use partly because interim data didn’t show a clear benefit in disease recurrence. The current win came from yet another interim analysis by an independent data monitoring committee.

“[W]e look forward to working with the FDA and other global authorities to bring this new option to patients as quickly as possible,” Roy Baynes, chief medical officer of Merck Research Laboratories, said in a statement.

RELATED: FDA snubs Keytruda in early breast cancer after harsh review as Merck looks to next data analysis

While Merck obviously hopes the updated event-free survival win could convince the FDA of Keytruda’s benefit in pre- and post-operative treatment settings, several uncertainties remain.

For one, staffers within the FDA and external breast cancer experts have voiced concerns that the surrogate tumor clearance marker Merck used to support Keytruda’s pre-surgery use wasn’t a good indicator of whether the therapy can extend patients' lives in this disease. Previously, the trial showed that 64.8% of patients who got the Keytruda-chemo combo before surgery had no residual cancer cells in resected tissues, only a 13.6-percentage-point improvement over solo chemo.

RELATED: FDA panel doesn't buy Merck's biomarker for fast Keytruda nod in TNBC, spelling trouble for other I-O meds

What’s more, the trial design that combined two so-called neoadjuvant and adjuvant treatment stages also raised eyebrows. The trial doesn’t answer, for example, the question of whether continued Keytruda use is necessary in patients who’ve already achieved complete pathologic response from pre-surgery treatment. Another ongoing phase 3 trial run by the National Cancer Institute is testing Keytruda specifically for the post-surgery adjuvant use in TNBC patients after neoadjuvant chemotherapy.

While the new event-free survival data can’t clarify those issues, they can at least better support Merck’s case with the FDA.

Expansion into early cancer settings is considered a key driver of growth for PD-1/L1 inhibitors like Keytruda. SVB Leerink analyst Daina Graybosch previously projected that about 50% of Keytruda growth through 2028 could come from the neoadjuvant and adjuvant settings.