Vibostolimab/Favezelimab Clinical Programs in NSCLC/Lymphoma Discontinued

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The phase 3 KeyVibe-003, KeyVibe-007, and KEYFORM-008 trials investigating vibostolimab and favezelimab have been discontinued.

The phase 3 KeyVibe-003, KeyVibe-007, and KEYFORM-008 trials investigating vibostolimab and favezelimab have been discontinued.

The phase 3 KeyVibe-003, KeyVibe-007, and KEYFORM-008 trials investigating vibostolimab and favezelimab have been discontinued.

Clinical development programs including the KeyVibe program investigating the anti–TIGIT antibody vibostolimab and the KEYFORM program investigating the anti–LAG-3 agent favezelimab have been discontinued, according to a press release from the developer, Merck.1

Data analyses for the phase 3 trials remain ongoing, and results, upon finalization, will be shared with the scientific community.

“Following a careful analysis of the data, the decision has been made to discontinue development of these candidates to prioritize other ongoing programs. We are grateful to all the patients, caregivers and investigators for their many contributions that made these studies possible,” Marjorie Green, MD, senior vice president and head of oncology, global clinical development at Merck, said in the press release.1 “We continue to pursue the most promising science with a focus on agents with the greatest potential to improve outcomes for more patients with cancer.”

The KeyVibe Program

The KeyVibe program consisted of the phase 3 KeyVibe-003 (NCT04738487) and KeyVibe-007 (NCT05226598) trials, which were evaluating a fixed-dose combination of vibostolimab with pembrolizumab (Keytruda) in specific patients with non–small cell lung cancer (NSCLC).

Both the KeyVibe-003 and the KeyVibe-007 trials met the pre-specified futility criteria for overall survival (OS), the primary end point, and demonstrated a safety profile for vibostolimab and pembrolizumab comparable to previous investigations. More immune-related adverse events (AEs) were experienced by patients who were administered the vibostolimab/pembrolizumab combo than pembrolizumab monotherapy.

KeyVibe-003 enrolled 1264 patients who were randomly assigned, in a 1:1 ratio, to receive either the fixed-dose combination (200 mg of intravenous vibostolimab and 200 mg of pembrolizumab) given every 3 weeks for up to 35 cycles, or 200 mg of intravenous pembrolizumab every 3 weeks for up to 35 cycles. The regimen served as a first-line therapy for patients with PD-L1–positive metastatic NSCLC.

KeyVibe-007 enrolled 739 patients who were randomly assigned, in a 1:1 ratio, to receive either the same fixed-dose combination plus platinum doublet chemotherapy once every 3 weeks for 4 cycles, then the fixed-dose combination for up to 31 cycles with maintenance pemetrexed at 500 mg/m2 once every 3 weeks for patients with a nonsquamous histology, or 200 mg of intravenous pembrolizumab plus platinum doublet chemotherapy once every 3 weeks for 4 cycles, then 200 mg of intravenous pembrolizumab for up to 31 cycles with maintenance pemetrexed every 3 weeks for patients with a nonsquamous histology. The regimen served as a therapy for treatment-naïve patients with metastatic NSCLC.

The phase 3 KeyVibe-006 trial (NCT05298423) investigating fixed-dose vibostolimab and pembrolizumab with concurrent chemoradiotherapy then vibostolimab and pembrolizumab compared with concurrent chemoradiotherapy then durvalumab (Imfinzi) in patients with stage III NSCLC was also discontinued.

Previously, the KeyVibe-010 (NCT05665595) trial investigating adjuvant vibostolimab with pembrolizumab compared with pembrolizumab monotherapy in patients with resected high-risk stage IIB to IV melanoma was discontinued in May 2024.2 The KeyVibe-008 trial (NCT05224141) investigating fixed-dose vibostolimab with pembrolizumab plus chemotherapy compared with pembrolizumab plus chemotherapy in patients with extensive-stage small cell lung cancer was also discontinued in August 2024.3

The KEYFORM Program

The KEYFORM program included the phase 3 KEYFORM-008 trial (NCT05508867), which evaluated a fixed-dose combination of favezelimab and pembrolizumab compared with physician’s choice of chemotherapy in patients with relapsed or refractory classical Hodgkin Lymphoma who experienced disease progression following anti–PD-1 therapy. The KEYFORM-008 trial was the only phase 3 trial in the program that did not have results available.

Patients in the KEYFORM-008 trial will be permitted to continue receiving the therapy regimen until study completion. The decision to discontinue the program comes after a review of the data that led developers to prioritize other agents and candidates in their pipeline. There were no concerns about the favezelimab/pembrolizumab combo’s safety data that factored into this decision.

KEYFORM-008 enrolled 169 patients who were randomly assigned, in a 1:1 ratio, to receive either 800 mg of intravenous favezelimab and 200 mg of intravenous pembrolizumab on day 1, then once every 3 weeks for up to 35 cycles, or physician’s choice of 90 to 120 mg/m2 of bendamustine (Treanda) on day 1 and 2 of a 3- or 4-week cycle for up to 6 cycles, or 800 to 1200 mg/m2 of gemcitabine (Gemzar) on day 1 and 8 once every 3 weeks for up to 6 cycles.

In the KEYFORM program, the phase 3 KEYFORM-007 trial (NCT05064059) investigating favezelimab with pembrolizumab in patients with previously treated PD-L1–positive microsatellite stable metastatic colorectal cancer did not meet its primary end point of OS at the final pre-specified analysis.4

References

  1. Merck provides update on KeyVibe and KEYFORM clinical development programs evaluating investigational vibostolimab and favezelimab fixed-dose combinations with pembrolizumab. News release. Merck. December 16, 2024. Accessed December 17, 2024. https://tinyurl.com/4jj5bkyu
  2. 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 December 17, 2024. https://tinyurl.com/2zeefcj2
  3. Merck provides update on phase 3 KeyVibe-008 trial evaluating an investigational fixed-dose combination of vibostolimab and pembrolizumab in patients with extensive- small cell lung cancer. News release. Merck. August 8, 2024. Accessed December 17, 2024. https://tinyurl.com/5fr4uwkt
  4. Merck provides update on phase 3 KEYFORM-007 trial evaluating investigational fixed-dose combination of favezelimab and pembrolizumab for patients with previously treated PD-L1positive microsatellite stable metastatic colorectal cancer. News Release. Merck. September 25, 2024. Accessed December 17, 2024. https://tinyurl.com/3d82mvr8
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