Merck Discontinues Phase III Trial of Keytruda Combination for SCLC

Merck has announced the discontinuation of the Phase III KeyVibe-008 trial evaluating a fixed-dose combination of vibostolimab and Keytruda (pembrolizumab) with chemotherapy compared to atezolizumab with chemotherapy for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). A pre-planned analysis revealed patients in the pembrolizumab-vibostolimab arm experienced a higher rate of adverse events (AEs) and immune-related AEs compared to those in the atezolizumab control arm.¹

Study investigators have been notified of the decision, will inform patients to discontinue treatment with the pembrolizumab-vibostolimab combination, and offer them to be treated with atezolizumab.

The Phase III KeyVibe-008 (NCT05224141) study is a randomized, double-blind trial. Its primary endpoint, which has now met its pre-specified futility criteria, is overall survival (OS). Key secondary endpoints include progression-free survival, objective response rate (ORR), and duration of response. The trial enrolled 460 patients.

In a press release, Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories said, “Small cell lung cancer remains a difficult disease to treat, as evident by the seven percent five-year survival rate and limited advancements in treatment options. Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease. We are extremely grateful to all of the patients, caregivers and investigators for their participation in this study.”

Daiichi Sankyo and Merck recently shared that the first patient has been dosed in the IDeate-Lung02 Phase III trial for relapsed SCLC, evaluating ifinatamab deruxtecan (I-DXd) versus treatment of physician’s choice of chemotherapy.²

According to Merck, I-DXd is a specifically engineered potential first-in-class B7-H3 directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo. It is being jointly developed by the two organizations.

The IDeate-Lung02 study (NCT06203210) is a global, multicenter, randomized, open-label trial. It has two primary endpoints—OS and ORR.

“The initiation of the IDeate-Lung02 trial for ifinatamab deruxtecan marks the second pivotal study since the start of our collaboration with Daiichi Sankyo and follows the recent initiation of the REJOICE-Ovarian01 Phase II/III study for raludotatug deruxtecan,” Green said in an earlier press release. “This is a significant milestone as we work together to evaluate an innovative medicine that may have the potential to make a meaningful difference in the lives of people facing small cell lung cancer, a difficult-to-treat cancer.”

For the treatment of non-small cell lung cancer (NSCLC), Merck announced in April that it had initiated a randomized, double-blind, multicenter Phase III trial (NCT06345729) of MK-1084, an investigational oral selective KRAS G12C inhibitor, in combination with pembrolizumab. The combo is being evaluated in patients with metastatic NSCLC whose tumors have KRAS G12C mutations and express PD-L1.³

“KRAS is among the most prevalent mutations in cancer and KRAS G12C is the most common KRAS mutation in patients with non-small cell lung cancer,” Green said. “Based on early evidence showing MK-1084 in combination with KEYTRUDA had a manageable safety profile and promising anti-tumor activity, we are now proceeding to a larger Phase III trial to evaluate this combination in certain patients with metastatic non-small cell lung cancer.”

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. IDeate-Lung02 Phase 3 Trial of Ifinatamab Deruxtecan Initiated in Patients With Relapsed Small Cell Lung Cancer. News release. Merck. August 1, 2024. Accessed August 8, 2024. https://www.merck.com/news/ideate-lung02-phase-3-trial-of-ifinatamab-deruxtecan-initiated-in-patients-with-relapsed-small-cell-lung-cancer/

3. Merck Initiates Phase 3 Clinical Trial of MK-1084, an Investigational Oral KRAS G12C Inhibitor, in Combination with KEYTRUDA® (pembrolizumab) for First-Line Treatment of Certain Patients With Metastatic Non-Small Cell Lung Cancer. News release. Merck. April 4, 2024. Accessed August 8, 2024. https://www.merck.com/news/merck-initiates-phase-3-clinical-trial-of-mk-1084-an-investigational-oral-kras-g12c-inhibitor-in-combination-with-keytruda-pembrolizumab-for-first-line-treatment-of-certain-patients-with-met/