Subcutaneous Pembrolizumab/Chemo Meets Pharmacokinetic Endpoints in NSCLC

For patients with NSCLC, subcutaneous pembrolizumab appeared noninferior vs intravenous pembrolizumab for study end points when combined with chemotherapy.

Subcutaneously administrated pembrolizumab (Keytruda) plus berahyaluronidase alfa (MK-3457A; “subcutaneous pembrolizumab”) administered with chemotherapy demonstrated noninferiority vs intravenous pembrolizumab with chemotherapy and met dual primary pharmacokinetic end points while remaining consistent in efficacy and safety for patients with metastatic non–small cell lung cancer (NSCLC) in the randomized, open-label phase 3 MK-3475A-D77 trial (NCT05722015), Merck announced in a press release.¹

During the trial, subcutaneous pembrolizumab given every 6 weeks with chemotherapy was noninferior compared with intravenous pembrolizumab plus chemotherapy for area under the curve (AUC) exposure of pembrolizumab during the first cycle of treatment. Additionally, trough concentration of subcutaneous pembrolizumab measured at steady state when compared with intravenous pembrolizumab with chemotherapy, as well.

Safety and efficacy, secondary end points of the trial, were also generally consistent for subcutaneous pembrolizumab with chemotherapy as with intravenous pembrolizumab with chemotherapy.

The developer continues to perform ongoing analyses and plans to present these data at an upcoming medical conference. They also plan to share these findings with regulatory authorities worldwide immediately.

Marjorie Green, MD, senior vice president and head of oncology, global clinic development, at Merck, said, “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 healthcare providers compared to intravenous administration.”¹

Primary trial end points were AUC of pembrolizumab measured after the first dose up to 14 months and trough concentration of pembrolizumab measured at steady state up to 18 months.

Additional secondary end points assessed were objective response rate per RECIST criteria, progression-free survival per RECIST, overall survival, duration of response per RECIST, maximum serum concentration of pembrolizumab measured after first dose, and trough concentration of pembrolizumab measured after first dose, among others.

An estimated 378 patients of age 18 or older were enrolled and randomly assigned in a 2:1 ratio to be administered either subcutaneous pembrolizumab with chemotherapy or intravenous pembrolizumab with chemotherapy.

Eligibility criteria include having a histologically or cytologically confirmed diagnosis of squamous or non-squamous NSCLC, an archival tumor tissue sample or excisional biopsy of a tumor lesion not previously irradiated, and a life expectancy of at least 3 months.²

Patients who had a diagnosis of small cell lung cancer or presence of small elements, had received prior systemic anticancer therapy for NSCLC, had received radiation therapy to the lung within 6 months of the study, and had an active autoimmune disease that has required systemic treatment in the past 2 years, among other criteria, were excluded from study participation.

The trial is a part of Merck’s ongoing subcutaneous pembrolizumab clinical development program. Also included in the program is the phase 3 MK-3475A-F84 trial (NCT06698042) analyzing the treatment of subcutaneous pembrolizumab alone compared with intravenous pembrolizumab alone as first-line therapy for patients with metastatic NSCLC; the phase 2 MK-3475A-F65 trial (NCT06504394) analyzing subcutaneous pembrolizumab administered alone in relapsed/refractory classical Hodgkin lymphoma and relapsed/refractory primary mediastinal large B-cell lymphoma; and the phase 2 MK-3475A-F11 study (NCT06099782) analyzing patient-reported preference for subcutaneous pembrolizumab compared with intravenous pembrolizumab.

“[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,” Green said in the press release.¹

References

1. Merck announces phase 3 trial of subcutaneous pembrolizumab with berahyaluronidase alfa met primary endpoints. News Release. Merck. November 19, 2024. Accessed on November 20, 2024. https://tinyurl.com/yw77tebs
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 20, 2024. https://tinyurl.com/2fak5w9w