KEY TAKEAWAYS
- MK-7684A-002 and KEYVIBE-002 phase 2 study aimed to evaluate MK-7684A (vibo + pembro) with/without docetaxel vs docetaxel alone in mNSCLC.
- The primary endpoint was PFS per RECIST v1.1 by BICR.
- The result concluded that MK-7684A + docetaxel for mNSCLC failed to outperform docetaxel alone in PFS and safety.
Patients with metastatic non-small-cell lung cancer (mNSCLC) often face a poor prognosis after progressing on anti-PD-(L)1 therapy with or after chemotherapy, creating a significant unmet need. The anti–T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) vibo, known for its antitumor activity alone and in combination with pembrolizumab (anti-PD-1), was assessed in the phase 2 KEYVIBE-002 study.
In this study, Nir Peled and his research group investigated MK-7684A, a coformulation of vibo and pembrolizumab, with or without docetaxel, compared to docetaxel alone in previously treated mNSCLC.
The interventional study enrolled Patients (pts) aged ≥18 years with pathologically confirmed mNSCLC, lacking EGFR/ALK/ROS1 alterations, experiencing disease progression after one prior anti-PD-(L)1 therapy (progression ≤12 weeks from last dose) and platinum-doublet chemotherapy, with measurable disease per RECIST v1.1, ECOG PS 0 or 1, and a tumor sample for PD-L1 assessment, were eligible. They were randomized 1:1:1 to receive MK-7684A (vibo 200 mg + pembro 200 mg) + docetaxel 75 mg/m² every 3 weeks (Arm 1; blinded), MK-7684A alone (Arm 2; open-label), or placebo + docetaxel (Arm 3; blinded).
The treatment continued for ≤35 cycles (∼2 years) for MK-7684A/placebo, following local guidelines for docetaxel, or until disease progression, unacceptable adverse events, or patient/physician decision. The primary endpoint was progression-free survival (PFS) per RECIST v1.1 by BICR. Safety served as a secondary endpoint of the study.
Around 87 pts were assigned to Arm 1, 83 to Arm 2, and 85 to Arm 3. The median follow-up was 12.3 months (range, 6.2–19.8). Median PFS (95% CI) was 5.6 months (3.9–6.8) in Arm 1, 2.7 months (1.8–4.0) in Arm 2, and 3.2 months (2.8–5.7) in Arm 3. The hazard ratio (HR) (95% CI) for PFS was 0.77 (0.53–1.13) for Arm 1 vs. Arm 3 (P = 0.0910) and 1.40 (0.96–2.02) for Arm 2 vs. Arm 3 (P = 0.9622).
Treatment-related adverse events (TRAEs) occurred in 82 pts (96.5%) in Arm 1, 50 (60.2%) in Arm 2, and 74 (89.2%) in Arm 3; fatalities were observed in 4 (4.7%), 1 (1.2%), and 1 (1.2%), respectively. Immune-mediated adverse events and infusion reactions occurred in 25 pts (29.4%), 17 (20.5%), and 10 (12.0%), respectively.
The study concluded that in pts with previously treated mNSCLC using anti-PD-(L)1 therapy and platinum-doublet chemotherapy, MK-7684A and MK-7684A + docetaxel did not exhibit statistically significant differences in PFS compared to docetaxel alone. Moreover, no new safety signals were observed. Ongoing follow-up will provide further insights.
This study is sponsored by Merck Sharp & Dohme LLC.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04725188
Peled N. et al. “MK-7684A (Vibostolimab [Vibo] Plus Pembrolizumab [Pembro] Coformulation) With/Without Docetaxel in Metastatic NSCLC After Platinum-Chemotherapy (Chemo) and Immunotherapy” presented at ESMO IO 2023. (Abstract: 121P)
