Coformulation of Pembrolizumab/Vibostolimab Fails to Show PFS Benefit in NSCLC

A statistically significant improvement in the primary end point of progression-free survival (PFS) failed to be generated with the coformulation of pembrolizumab (Keytruda) and vibostolimab (MK-7684A) compared with docetaxel in pretreated patients with metastatic non–small cell lung cancer (NSCLC), according to results from the open-label arm of the phase 2 KeyVibe-002 trial (NCT04725188).¹

The coformulation of pembrolizumab and vibostolimab also was numerically less effective than docetaxel. Merck is informing investigators on the trial that patients receiving MK-7684A arm should be switched to standard-of-care docetaxel, unless physicians believe patients are benefiting from MK-7684A alone.

Pembrolizumab and vibostolimab in combination with docetaxel will continue to be evaluated compared with docetaxel and placebo in blinded arms of the study as planned, and full data from the trial will be presented at an upcoming medical meeting when findings 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,” said 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 which works to restore antitumor activity. The agent blocks the TIGIT receptor from binding to the CD112 and CD155 ligands 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.

In the KeyVibe-002 trial, investigators examined the coformulation of pembrolizumab plus vibostolimab with or without docetaxel vs docetaxel plus placebo in patients with NSCLC who experienced progressive disease following treatment with immunotherapy and platinum-doublet chemotherapy.²

A total of 255 patients were enrolled and randomized 1:1:1 between the 3 treatment arms. In the open-label arm A, patients were treated intravenously (IV) with 200 mg of pembrolizumab plus 200 mg/20 mL of vibostolimab every 3 weeks for up to 35 cycles. In the blinded arm B, patients were given the same regimen in addition to 75 mg/m2 of IV docetaxel every 3 weeks. Then, those in blinded arm C were treated with placebo plus the same docetaxel regimen every 3 weeks.

Enrollment in the trial was open to patients aged 18 years and older with a histologically or cytologically confirmed diagnosis of metastatic NSCLC with EGFR, ALK, or ROS 1-directed therapy is not indicated as primary therapy. Patients must have had progressive disease (PD) on treatment with 1 prior anti-PD-1/PD-L1 monoclonal antibody given as either alone or in combination with other checkpoint inhibitors or other therapies.

Other enrollment criteria included having PD as determined by the investigator after platinum doublet chemotherapy for metastatic disease, measurable disease defined as at least 1 measurable lesion by CT or MRI, based on RECIST 1.1, a life expectancy of at least 3 months, and an ECOG performance status of 0 to 1, and provide tumor tissue for PD-L1 biomarker analysis from an archival sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.

The primary end point was PFS assessed by blinded independent central review (BICR) per RECIST v1.1 criteria, and secondary end points consisted of overall survival and objective response rate assessed by BICR per RECIST v1.1 criteria, to evaluate the efficacy of the addition of the pembrolizumab/vibostolimab coformulation to docetaxel vs docetaxel alone.

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

Reference

1. 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. Merck. March 16, 2023. Accessed March 17, 2023. https://bit.ly/3FvV0xR

2. Pembrolizumab/vibostolimab coformulation (MK-7684A) or pembrolizumab/vibostolimab coformulation plus docetaxel versus docetaxel for metastatic non small cell lung cancer (NSCLC) with progressive disease after platinum doublet chemotherapy and immunotherapy (MK-7684A-002, KEYVIBE-002). ClinicalTrials.gov. Updated January 5, 2023, Accessed March 17, 2023. https://clinicaltrials.gov/ct2/show/study/NCT04725188