For patients with previously untreated metastatic non–small cell lung cancer (NSCLC), treatment with Keytruda (pembrolizumab) plus berahyaluronidase alfa (subcutaneous Keytruda; MK-3475A) in combination with chemotherapy met pharmacokinetics (PK) end points of the phase 3 MK-3475A-D77 trial, according to a press release from Merck.
The noninferiority of subcutaneous Keytruda plus chemotherapy versus the intravenous (IV) formulation of Keytruda plus chemotherapy was evaluated in the first-line setting of this randomized, open-label study for patients with metastatic NSCLC.
The press release shared that the subcutaneous formulation of Keytruda — given every six weeks — plus chemotherapy demonstrated noninferiority in area under the curve exposure of Keytruda during the first dosing cycle, as well as noninferiority in trough concentration (Ctrough) of Keytruda measured at steady state when compared with the IV formulation of Keytruda given every six weeks in combination with chemotherapy. As such, the investigative combination of subcutaneous Keytruda and chemotherapy met the pharmacokinetic (PK) end points of the MK-3475A-D77 trial.
Secondary end points of efficacy and safety were generally consistent with the subcutaneous combination therapy versus the IV combination therapy. Notably, Merck stated in the press release that these results, as well as other findings from ongoing analyses, will be shared at an upcoming medical meeting and with regulatory authorities worldwide.
“Keytruda 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,” Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, at Merck Research Laboratories, explained in the 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 two to three minutes and has the potential to improve the patient experience as well as increase access for patients and healthcare providers compared to intravenous administration.”
In the MK-3475A-D77 clinical trial, patients with metastatic NSCLC were enrolled. Eligible patients included those 18 years of age or older who presented with histologically or cytologically confirmed squamous or nonsquamous NSCLC; these individuals must also have had a life expectancy of at least three months. Additionally, treatment with prior systemic therapies for their disease were not allowed within four weeks of randomization, including radiotherapy within two weeks of the start of the study.
Eligible participants were enrolled and randomly assigned 2:1 to treatment with subcutaneous Keytruda and berahyaluronidase alfa, administered every six weeks, with chemotherapy, versus IV Keytruda, also administered every six weeks, in combination with chemotherapy in the first-line setting. Investigators aimed to assess the dual primary PK end points of area under the curve of Keytruda exposure during the first dosing cycle and the Ctrough of Keytruda measured at steady state. Secondary end points included additional PK parameters, as well as efficacy end points, including objective response rate, duration of response, progression-free survival and overall survival, as well as safety. Notably, an estimated 378 patients were enrolled onto the investigation.
The press release goes on to share how Keytruda works. The anti-PD–1 therapy increases the ability of the body’s immune system, which is done to help in the detection and fight of tumor cells. The IV formulation of Keytruda is a humanized monoclonal antibody that works by blocking the interaction between PD-1 and its ligands, PD- L1 and PD-L2. This thereby activates T lymphocytes which may affect both tumor cells and healthy cells.
“We plan to discuss these results with regulatory authorities worldwide as soon as possible,” Dr. Green concluded in the press release.
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