Vibostolimab/Pembrolizumab Coformulation Fails to Reach PFS End Point in Pretreated Metastatic NSCLC

A coformulation of pembrolizumab (Keytruda) and vibostolimab (MK-7684A) did not elicit a statistically significant improvement in progression-free survival (PFS) vs docetaxel in pretreated patients with metastatic non–small cell lung cancer (NSCLC), according to results from the open-label portion of the phase 2 KeyVibe-002 trial (NCT04725188).

The coformulation was also numerically less effective than docetaxel, and Merck is notifying study investigators that patients in the MK-7684A arm should be switched to standard-of-care docetaxel, unless patients are benefiting from MK-7684A alone in the eyes of their physician.

The blinded arms of the trial evaluating MK-7684A in combination with docetaxel vs docetaxel and placebo will continue as planned. Full results from the trial will be presented at an upcoming medical meeting when further data from the blinded arms are available.

“Through different approaches, such as novel combinations and coformulations, we hope to build on the foundation of [pembrolizumab] to help even more patients with cancer,” Eliav Barr, MD, senior vice president, head of Global Clinical Development, and chief medical officer, at Merck Research Laboratories, stated in a news release. “We are grateful to the patients and investigators for their participation in this study evaluating MK-7684A in a heavily pretreated group of patients and look forward to additional data from the continuation of the blinded arms of KeyVibe-002. Based on responses we have seen in the signal-finding phase 1/2 program to date, we are moving forward with our comprehensive research program evaluating MK-7684A across a wide range of cancers, including lung, other solid tumors and blood cancers.”

Vibostolimab is a humanized anti-TIGIT therapy that restores antitumor activity by blocking the TIGIT receptor from binding to the CD112 and CD155 ligands in order to activate T lymphocytes that help destroy tumor cells. MK-7684A is a coformulation of both vibostolimab and pembrolizumab being evaluated in lung cancer, other solid tumors, and blood cancers.

KeyVibe-002 evaluated the coformulation of pembrolizumab/vibostolimab with or without docetaxel vs docetaxel and placebo in patients with NSCLC who experienced progressive disease after treatment with immunotherapy and platinum-doublet chemotherapy. The study examined the efficacy of MK-7684A alone compared with docetaxel, and, in a blinded assessment, evaluated the efficacy of adding MK-7684A to docetaxel vs docetaxel alone.

The trial enrolled 255 patients who were randomly assigned 1:1:1 between the 3 treatment arms. Patients in the open-label arm A were treated with intravenous (IV) MK-7684A, consisting of 200 mg of pembrolizumab plus 200 mg/20 mL of vibostolimab every 3 weeks for up to 35 cycles. Those in the blinded arm B received the same MK-7684A regimen plus 75 mg/m² of IV docetaxel every 3 weeks. Patients in the blinded arm C were given placebo plus the same docetaxel regimen every 3 weeks.

Along with the primary end point of PFS assessed by blinded independent central review (BICR) per RECIST v1.1 criteria, secondary end points included overall survival and objective response rate assessed by BICR per RECIST v1.1 criteria.

Regarding safety, the toxicity profile of MK-7684A was consistent with previously observed findings for vibostolimab and pembrolizumab in prior studies, and no new safety signals were observed.

Reference

Merck provides update from open-label arm of phase 2 KeyVibe-002 trial evaluating MK-7684A, a coformulation of vibostolimab and pembrolizumab, in previously treated patients with metastatic non-small cell lung cancer (NSCLC). News release. March 16, 2023. Accessed March 17, 2023. https://www.merck.com/news/