Subcutaneous Pembrolizumab Is Noninferior to IV Formulation in NSCLC

Subcutaneous pembrolizumab plus chemotherapy was noninferior to IV pembrolizumab plus chemotherapy in treatment-naïve non-small cell lung cancer.

Pembrolizumab (Keytruda) and berahyaluronidase alfa (subcutaneous pembrolizumab; MK-3475A) plus chemotherapy demonstrated noninferior pharmacokinetics (PK) compared with the intravenous (IV) formulation of pembrolizumab plus chemotherapy in adults with previously untreated metastatic non–small cell lung cancer (NSCLC), according to topline findings from the phase 3 MK-3475A-D77 trial (NCT05722015).¹

The randomized, open-label trial investigated the noninferiority of subcutaneous pembrolizumab plus chemotherapy vs IV pembrolizumab and chemotherapy given in the first-line for patients with metastatic NSCLC.

PK findings showed that the subcutaneous formulation plus chemotherapy demonstrated noninferiority in area under the curve (AUC) exposure of pembrolizumab during the first dosing cycle and noninferiority in trough concentration (Ctrough) at a steady.

Regarding data for secondary end points, which focused on efficacy and safety, findings for subcutaneous pembrolizumab plus chemotherapy were generally consistent compared with IV pembrolizumab plus chemotherapy.

Results from MK-3475A-D77 and data from other ongoing analyses will be presented at an upcoming medical meeting and shared with global regulatory authorities.

“[Pembrolizumab] has helped transform the way we treat some of the deadliest forms of cancer, yet we continue to pursue additional innovations that may benefit patients,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, stated in the news release. “It is very encouraging to see positive phase 3 results evaluating this fixed-dose combination of subcutaneous pembrolizumab, which was administered, on average, in approximately 2 to 3 minutes and has the potential to improve the patient experience as well as increase access for patients and health care providers compared [with] intravenous administration.”

MK-3475A-D77 was an open-label, randomized study that included patients at least 18 years of age with histologically or cytologically confirmed squamous or nonsquamous NSCLC who had a life expectancy of at least 3 months.² Patients were not allowed to receive any prior systemic anticancer therapy for metastatic NSCLC or prior systemic anticancer therapy—including investigational agents—within 4 weeks of randomization. Radiotherapy within 2 weeks of the start of the study was not allowed, and patients could not have any radiation-related toxicities requiring corticosteroids.

Approximately 378 patients were enrolled and randomly assigned in a 2:1 fashion to receive either subcutaneous pembrolizumab with chemotherapy or IV pembrolizumab with chemotherapy.¹

The 2 primary end points of the trial were AUC of pembrolizumab exposure during the first dosing cycle and the Ctrough of pembrolizumab at steady state. Secondary end points included additional PK parameters; efficacy outcomes such as objective response rate, duration of response, progression-free survival, and overall survival; and safety.

Merck’s subcutaneous pembrolizumab clinical development program also includes the phase 3 MK-3475A-F84 trial (NCT04956692), which is investigating subcutaneous pembrolizumab alone compared with IV pembrolizumab alone in the first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression, defined as a tumor proportion score of at least 50%.¹

The phase 2 MK-3475A-F65 trial (NCT06504394) is evaluating subcutaneous pembrolizumab alone in relapsed/refractory classical Hodgkin lymphoma and relapsed/refractory primary mediastinal large B-cell lymphoma. The phase 2 MK-3475A-F11 trial (NCT06099782) will evaluate patient-reported preferences for subcutaneous pembrolizumab vs IV pembrolizumab across multiple tumor types.

References

1. Merck announces phase 3 trial of subcutaneous pembrolizumab with berahyaluronidase alfa met primary endpoints. News release. Merck. November 19, 2024. Accessed November 19, 2024. https://www.merck.com/news/merck-announces-phase-3-trial-of-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-met-primary-endpoints/

2. A study of subcutaneous (SC) pembrolizumab coformulated with hyaluronidase (MK-3475A) vs intravenous pembrolizumab in adult participants with metastatic non-small cell lung cancer (NSCLC) (MK-3475A-D77). ClinicalTrials.gov. Updated February 28, 2024. Accessed November 19, 2024.