Merck & Co.’s subcutaneous (SC) formulation of Keytruda has matched up to the original intravenous (IV) version on two blood concentration measurements, paving way for a potential FDA approval that could give patients a more convenient option of the widely used cancer drug.
Keytruda SC was noninferior to Keytruda IV in terms of overall drug exposure during the first cycle of treatment, as well as steady-state trough concentration during cycle 3, according to phase 3 data presented at the European Lung Cancer Congress 2025.
The data came from the pivotal 3475A-D77 trial, which evaluated the Keytruda versions in their separate combinations with chemotherapy in patients with newly diagnosed metastatic non-small cell lung cancer. As Merck previously announced, the two pharmacokinetics measurements serve as dual primary endpoints of the study.
On both endpoints, Keytruda SC appeared to perform better than IV. The comparison’s geometric mean ratio was 1.14 for the cycle 1 Area Under the Curve marker, and 1.67 for the cycle 3 Ctrough endpoint, both coming above the 0.8 bar for noninferiority. A figure above 1 indicates higher concentration for Keytruda SC than for IV.
Those comparable blood concentrations also translated into similar efficacy. After a median follow-up of 9.6 months, the risk of disease progression or death was similar, with a marginal 5% in favor of IV. Patient survival results instead favored SC, with a 19% improvement. These numbers are descriptive and do not carry statistical significance to declare one formulation better than the other.
Keytruda SC also showed a safety profile that’s consistent with IV. Grade 3 or above treatment-related adverse events happened in 47% of patients who received the under-the-skin version and chemo, versus 47.6% for the IV-chemo group. These included 3.6% and 2.4% of deaths in the SC arm and IV arm, respectively.
Roughly 1% of patients in both arms developed antidrug antibodies following treatment.
Based on the results, the FDA has accepted Merck’s application for Keytruda SC to cover all existing solid tumor indications of Keytruda IV, and the agency has set Sept. 23, 2025, as the target decision date.
Merck plans to launch Keytruda SC this year, CEO Rob Davis said at the J.P. Morgan Healthcare Conference in January. But the New Jersey pharma’s ability to commercialize the new formulation may depend on the outcome of a patent fight with drug delivery specialist Halozyme Therapeutics.
Halozyme has alleged that the human hyaluronidase protein used in Keytruda SC infringes its Mdase portfolio of patents. Merck licenses the protein, called berahyaluronidase alfa, from Alteogen.
Merck has filed a petition with the U.S. Patent and Trademark Office to challenge seven of Halozyme’s patents. Halozyme said it had reached out to Merck for a licensing arrangement and would seek an injunction preventing Merck from commercializing Keytruda SC through a lawsuit if the two companies couldn’t agree on a deal.
Keytruda SC comes with a convenience edge. In the 3475A-D77 trial, the median injection time for Keytruda SC was just two minutes. By comparison, the IV form typically takes about 30 minutes to administer.
Patient time in chair during treatment with Keytruda was nearly halved to 59 minutes with the SC injection, versus 117 minutes with IV, according to a prospective analysis. The time spent on chemotherapy administration was not included in this calculation. For healthcare providers, the SC version was also linked to a 46% reduction in time spent on preparation, administration process and patient monitoring.
“If approved, we are excited about the potential of subcutaneous [Keytruda] to become a new meaningful treatment option that may increase access and save time needed for administration compared to IV Keytruda,” Marjorie Green, head of oncology global clinical development at Merck Research Laboratories, said in a statement Thursday.
Although Merck tested Keytruda SC alongside chemo to win regulatory approvals, this isn’t the treatment setting in which the company expects the injection will garner the most interest. Instead, Merck believes Keytruda monotherapy or its combination with oral drugs will represent the majority of SC use because the need for other infused drugs, such as chemo, will cancel out the injection’s convenience edge.
Before Merck, Roche’s Tecentriq and Bristol Myers Squibb’s Opdivo both have subcutaneous formulations approved by the FDA.