Investigators Discontinue Vibostolimab Combo in Resected Melanoma Trial

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The phase 3 KeyVibe-010 trial is unlikely to meet its primary end point of recurrence-free survival due to a high rate of treatment discontinuation.

In the double-blind phase 3 KeyVibe-010 trial (NCT05665595), 1594 patients with resected high-risk stage IIB to IV melanoma were randomly assigned 1:1 to receive either vibostolimab/pembrolizumab or pembrolizumab monotherapy.

In the double-blind phase 3 KeyVibe-010 trial (NCT05665595), 1594 patients with resected high-risk stage IIB to IV melanoma were randomly assigned 1:1 to receive either vibostolimab/pembrolizumab or pembrolizumab monotherapy.

Investigators will discontinue their assessment of a coformulation including vibostolimab in combination with pembrolizumab (Keytruda) as adjuvant therapy for patients with resected high-riskstage IIB to IV melanoma as part of the phase 3 KeyVibe-010 trial (NCT05665595), according to a press release from the developers, Merck.1

The trial’s primary end point of recurrence-free survival (RFS) reached the pre-specified futility criteria based on a pre-planned analysis. The experimental coformulation had a small likelihood of producing a statistically significant RFS improvement due to a high rate of treatment discontinuation among patients who received the combination vs those who received pembrolizumab monotherapy. Most patients in the coformulation arm discontinued treatment following immune-mediated adverse effects (AEs).

Developers will unblind the study per the independent data monitoring committee recommendation. Additionally, those who are receiving the vibostolimab/pembrolizumab coformulation are recommended to cross over to pembrolizumab monotherapy.

Investigators are conducting a data analysis and will present their findings to the scientific community and regulatory health authorities.

“Through our clinical development program, we continue to ask the tough questions in an effort to fully explore the potential of novel coformulations and combinations that build on the foundation of [pembrolizumab], with a goal to improve upon current standards of care and help even more patients with cancer,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck Research Laboratories, said in the press release.1

In the double-blind phase 3 KeyVibe-010 trial, 1594 patients with resected high-risk stage IIB to IV melanoma were randomly assigned 1:1 to receive either vibostolimab/pembrolizumab or pembrolizumab monotherapy. In the coformulation arm, patients received pembrolizumab at 200 mg/20mL and vibostolimab at 200 mg intravenously every 3 weeks for a maximum of 17 cycles. In the monotherapy arm, investigators administered pembrolizumab at 200 mg to adult patients every 3 weeks for up to 17 cycles; adolescent patients of at least 40 kg received the agent at 2 mg/kg in this arm.

The trial’s secondary end points included distant metastasis-free survival, overall survival, and adverse effects.2 The trial also evaluated changes in global health status, physical functioning, and role functioning based on various European Organization for Research and Treatment of Cancer questionnaires.

Patients 12 years and older with histologically or pathologically confirmed cutaneous melanoma who received no prior systemic therapy beyond surgical resection were eligible for enrollment on the trial. Additional eligibility criteria included having no more than 12 weeks between the time of final surgical resection and randomization. Those with human immunodeficiency virus must have been treated with anti-retroviral therapy to enroll on the trial.

Those with ocular, mucosal, or conjunctival melanoma or no adequate recovery from prior major surgical procedures were unable not eligible to enroll on the trial. Patients were also unsuitable for enrollment if they had prior radiotherapy within 2 weeks of entry, a live attenuated virus within 30 days of beginning treatment, known central nervous system metastases and/or carcinomatous meningitis, an active autoimmune disease requiring systemic therapy in the last 2 years, or active infection that needed to be managed with systemic therapy. Having an allogenic tissue or solid organ transplant was also grounds for exclusion from the trial.

According to the press release, treatment with the vibostolimab/pembrolizumab coformulation in patients with lung cancer is currently under assessment as part of the phase 3 KeyVibe-003 trial (NCT04738487), phase 3 KeyVibe-006 trial (NCT05298423), phase 3 KeyVibe-007 trial (NCT05226598), and phase 3 KeyVibe-008 trial (NCT05224141). Developers do not intend to modify the designs of these studies following results from the KeyVibe-010 trial.

References

  1. Merck provides update on phase 3 KeyVibe-010 trial evaluating an investigational coformulation of vibostolimab and pembrolizumab as adjuvant treatment for patients with resected high-risk melanoma. News release. Merck. May 13, 2024. Accessed May 14, 2024. https://tinyurl.com/2zeefcj2
  2. A Study of adjuvant pembrolizumab/vibostolimab (MK-7684A) versus pembrolizumab for resected high-risk melanoma in participants with high-risk stage II-IV melanoma (MK-7684A-010/KEYVIBE-010). ClinicalTrials.gov. Accessed May 14, 2024. https://tinyurl.com/3huucp7b
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