FDA Approves First Subcutaneous Version of Keytruda for Adults With Most Solid Tumors

The FDA approved Merck’s Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) injection Friday for subcutaneous use in adults, expanding access to the widely used cancer therapy with a faster, less invasive option than the traditional intravenous use.

Keytruda Qlex is now the first and only subcutaneously administered immune checkpoint inhibitor available in the U.S. that can be given by a healthcare provider in as little as one minute every three weeks, or two minutes every six weeks, compared with the roughly 30 minutes needed for an intravenous (IV) infusion of Keytruda.

Unlike intravenous administration, which delivers the drug directly into a vein through an infusion, a subcutaneous injection is given just under the skin using a short needle, allowing for quicker delivery in a less invasive manner.

Merck expects to make the new formulation available before the end of September, according to a news release.

The FDA’s decision applies across most of the 38 tumor indications for which IV Keytruda is already approved, making the subcutaneous version more convenient for a wide range of patients. These cancer indications include non-small cell lung cancer (NSCLC), melanoma, head and neck cancers and others where immunotherapy has become part of standard treatment.

J. Thaddeus Beck, M.D., an oncologist and medical director of the Highlands’ Clinical Trials Office, noted the approval was “significant” for patients and providers, including himself, who have been using immunotherapies for years to treat certain cancers.

“We now have a new option with a broad set of indications that has demonstrated comparability with intravenous (IV) pembrolizumab but in a subcutaneous injection that can be administered in one minute every three weeks or two minutes every six weeks,” Beck said, adding that subcutaneous delivery “provides faster administration than IV pembrolizumab, offers two dosing options and gives patients more choices of healthcare settings in which they can receive their therapy.”

The FDA’s decision was supported by Study 3475A-D77, a multicenter, randomized phase 3 trial that compared Keytruda Qlex given with chemotherapy to IV Keytruda with chemotherapy in patients with advanced metastatic non-small cell lung cancer that had not yet been treated or who had no EGFR, ALK or ROS1 genomic tumor aberrations.

The trial enrolled 377 patients, randomized in a 2:1 ratio. Those in the Keytruda Qlex arm received a 790 mg/9,600 unit injection every six weeks along with chemotherapy (251 patients), while those in the IV arm (126 patients) received the standard 400 mg infusion every six weeks plus chemotherapy.

The primary endpoint measured how much pembrolizumab was present in the body over time, using pharmacokinetic markers such as the area under the curve (AUC) in the first six weeks and trough concentrations by the third cycle. Results showed similar drug exposure levels between the two formulations.

In addition, both groups showed nearly the same results.

The overall response rate was 45% in the Keytruda Qlex arm versus 42% in the IV arm. According to trial data, there were “no notable differences” in progression-free survival and overall survival between groups.

Safety findings were also consistent with prior experience using IV Keytruda. The most common adverse reactions in patients who received Keytruda Qlex with chemotherapy were nausea (25%), fatigue (25%) and musculoskeletal pain (21%). Serious adverse events occurred in 39% of patients in the Keytruda Qlex arm, with pneumonia being the most frequent at 10%.

Patient advocates also welcomed the option.

For example, Sally Werner, CEO of Cancer Support Community, expressed that the approval reflects the kind of patient-centered progress her organization supports.

“As part of supporting patients and families through their cancer journeys, we are excited to see patient-focused developments in subcutaneous cancer treatment that shorten administration time and may allow for more patients to receive treatment in multiple health care settings,” Werner said.

For patients, the option could ease some of the burdens of treatment.

For instance, subcutaneous injections can often be given in local clinics or community practices, reducing the need to travel to specialized infusion centers. This flexibility may be especially valuable for people with limited access to care or those who have difficulty with IV lines.

Merck has not yet announced the price for Keytruda Qlex, though the intravenous version of Keytruda carries a list price of about $200,000 per year. It was also found in a study published in the International Journal of Clinical Practice that subcutaneous administration can cut administration costs by about half compared to intravenous infusions.