Late-Stage Vibostolimab, Pembrolizumab Plus Chemotherapy Trial Discontinued Due to Adverse Events

Merck announced today that it would be discontinuing its late-stage trial for vibostolimab/pembrolizumab plus chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC).¹ The anti–PD-1 therapy was being compared with atezolizumab in combination with chemotherapy in the KeyVibe-008 trial (NCT05224141). However, patients on vibostolimab/pembrolizumab had a higher rate of adverse events (AEs) and immune-related AEs compared with the control arm, leading to its discontinuation.

Vibostolimab is one of several immunotherapies defined as anti-TIGIT. This new class of immunotherapies has been popular for drugmakers, as it has the potential to change how cancer is treated. However, the few trials in the space have been less successful. Anti-TIGIT drugs work by binding themselves to TIGIT, which is a receptor on immune cells.² The drug then helps to activate the immune system against cancer cells while preventing an immune attack against healthy cells.

The combination of vibostolimab and pembrolizumab proved to be unsafe in patients with small cell lung cancer | Image credit: Sebastian Kaulitzki - stock.adobe.com

In previous tests, this combination failed to slow disease progression in patients with lung cancer who had not responded to other treatments and in patients with severe skin cancer. All participants in the study will immediately cease use of the treatment immediately.

The trial was a randomized, double-blind study³ that enrolled patients who were 18 years and older with confirmed stage IV ES-SCLC. All participants needed to have a predicted life expectancy of at least 3 months. Patients were excluded if they had poor medical risk, had prior treatment for SCLC, had a live or live-attenuated vaccine within 30 days of the study, and had a history of noninfectious pneumonitis interstitial lung disease, among other exclusion criteria.

All participants in the experimental group received 200 mg of vibostolimab and 200 mg of pembrolizumab, plus etoposide and platinum chemotherapy once every 3 weeks for 4 cycles. The other group received 1200 mg of atezolizumab in combination with etoposide and platinum chemotherapy once every 3 weeks for 4 cycles before transitioning to atezolizumab by itself. Participants were allowed to stay in the trial until they met grounds for discontinuation.

This cancellation calls into question other ongoing studies involving anti-TIGIT therapies, including the phase 3 studies KeyVibe-003 (NCT04738487), KeyVibe-006 (NCT0529842), and KeyVibe-007 (NCT05226598). Although several companies, such as Gilead Sciences and GSK, are looking into vibostolimab and pembrolizumab as the future of treatment in lung cancer, no previous study has seen any improvement in progression-free or overall survival, and others, such as the KeyVibe-010 trial, have been discontinued. KeyVibe-003 and KeyVibe-006 are both looking into non–small cell lung cancers (NSCLCs) to assess efficacy in that subgroup. These trials are scheduled for completion in 2026, so it remains unknown what the efficacy of either treatment will be.

Although past clinical trials have seen lackluster results, it’s worth looking forward to the results of the clinical trials on the way, as a breakthrough on these treatments could spell a new direction in lung cancer treatment, especially in NSCLC. However, this discontinuation does throw another blow to the use of these therapies in the future.

References

1. Merck provides update on phase 3 KeyVibe-008 trial evaluating an investigational fixed-dose combination of vibostolimab and pembrolizumab in patients with extensive-stage small cell lung cancer. News release. Merck. August 8, 2024. Accessed August 8, 2024. https://www.merck.com/news/merck-provides-update-on-phase-3-keyvibe-008-trial-evaluating-an-investigational-fixed-dose-combination-of-vibostolimab-and-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer/

2. Merck stops testing combo drug for lung cancer. Reuters. August 8, 2024. Accessed August 8, 2024. https://www.reuters.com/business/healthcare-pharmaceuticals/merck-stops-experimental-lung-cancer-drug-combo-trial-2024-08-08/

3. Ryan C. Merck discontinues KeyVibe-008 trial of vibostolimab/pembrolizumab plus chemo in ES-SCLC. OncLive^®. August 8, 2024. Accessed August 8, 2024. https://www.onclive.com/view/merck-discontinues-keyvibe-008-trial-of-vibostolimab-pembrolizumab-plus-chemo-in-es-sclc