The FDA Approval of Keytruda Qlex: A Subcutaneous Version of Pembrolizumab

The FDA approved pembrolizumab and berahyaluronidase alfa-pmph subcutaneous injection (Keytruda Qlex; Merck) on September 19, 2025, for adult and pediatric patients 12 years and older with solid tumors, for indications already approved for intravenous (IV) pembrolizumab.¹ Pembrolizumab is a humanized monoclonal antibody that belongs to a class of medications called immune checkpoint inhibitors. Pembrolizumab works by removing the “brakes” on the body’s immune system, allowing it to attack cancer cells. It binds to a protein called PD-1 on T cells, a critical component that cancer cells use to evade the immune system.

By blocking this pathway, pembrolizumab allows the immune system to recognize and destroy cancer cells. Berahyaluronidase alfa is added to pembrolizumab to enable rapid administration and enhance subcutaneous absorption.

The approval of Keytruda Qlex was based on data from the randomized, multicenter, open-label MK-3475A-D77 study (NCT05722015)² of the active-controlled pharmacokinetics, efficacy, and safety of Keytruda Qlex in combination with chemotherapy vs pembrolizumab in combination with chemotherapy for the first-line treatment of patients with metastatic non–small cell lung cancer. The primary outcome measure was exposure to Keytruda Qlex compared with pembrolizumab, with additional efficacy outcomes including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 377 patients were enrolled and randomly assigned 2:1 to receive either Keytruda Qlex (administered subcutaneously every 6 weeks) with platinum doublet chemotherapy or pembrolizumab (administered IV every 6 weeks) with platinum doublet chemotherapy.¹

With regard to outcomes, the overall exposure and trough concentrations of Keytruda Qlex were noninferior to IV pembrolizumab, and there were no notable differences in PFS or OS. The ORR was 45% in the Keytruda Qlex arm (95% CI, 39-52) compared with 42% in the IV pembrolizumab arm (95% CI, 33-51). The PFS was 8.1 months in the Keytruda Qlex arm vs 7.8 months for IV pembrolizumab. Additionally, the overall safety profile was consistent between Keytruda Qlex plus chemotherapy and pembrolizumab plus chemotherapy.¹

The incidence of treatment-related adverse events (AEs), grade 3 to 5 treatment-related AEs, and serious treatment-related AEs was similar between arms. Patients should be monitored for signs and symptoms of immune-mediated adverse reactions. Liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically throughout treatment, and additionally as clinically warranted.¹

Keytruda Qlex is approved for 38 indications across 16 cancer types, but importantly, it is not currently FDA approved for classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma. Keytruda Qlex is a ready-to-use solution with dosing of 395 mg every 3 weeks or 790 mg every 6 weeks. Of note, the dosing is not the same as IV pembrolizumab doses. The dose, frequency, and duration of treatment are determined by indication. Patients may switch from pembrolizumab to Keytruda Qlex at their next scheduled dose.³

As far as administration, Keytruda Qlex is administered subcutaneously by a health care professional into the thigh or abdomen; the 5-cm area around the navel should be avoided. The every-3-week dosing is 395 mg of pembrolizumab and 4800 units of berahyaluronidase alfa (equivalent to 2.4 mL), which can be administered subcutaneously over 1 minute. The 6-week dosing schedule is 790 mg of pembrolizumab and 9600 units of berahyaluronidase alfa (equivalent to 4.8 mL) to be administered subcutaneously over 2 minutes. Treatment is continued until disease progression, unacceptable toxicity, or as indicated in the prescribing information.³

In summary, the decision to switch from pembrolizumab to Keytruda Qlex is a personal choice that depends on a patient’s specific treatment plan and medical needs. If a patient is receiving other IV medications, such as chemotherapy or immunotherapy, it would make more sense to administer IV pembrolizumab. In patients on single-agent pembrolizumab, in the maintenance setting, or on concurrent oral therapies, the convenience of Keytruda Qlex, a subcutaneous product, provides an additional option.

REFERENCES

1. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. FDA. September 19, 2025. Accessed February 4, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection

2. A study of subcutaneous (SC) pembrolizumab coformulated with berahyaluronidase alfa (MK-3475A) vs Intravenous pembrolizumab in adult participants with metastatic non-small cell lung cancer (NSCLC) (MK-3475A-D77). ClinicalTrials.gov. Updated September 11, 2025. Accessed February 5, 2026. https://www.clinicaltrials.gov/study/NCT05722015

3. Keytruda Qlex. Prescribing information. Merck Sharp & Dohme LLC; 2026. Accessed March 5, 2026. https://www.merck.com/product/usa/pi_circulars/k/keytruda_qlex/keytruda_qlex_pi.pdf