Combination of vibostolimab and pembrolizumab is well tolerated and has antitumor activity.
Major Finding: Combination of vibostolimab and pembrolizumab is well tolerated and has antitumor activity.
Concept: This phase I first-in-human trial demonstrated no dose-limiting toxicities but some treatment-related adverse events.
Impact: Further investigation into the efficacy of this combination in advanced solid tumors is supported.
Checkpoint inhibition has revolutionized cancer treatment especially in non–small cell lung cancer (NSCLC), but increased resistance to these therapies remains an issue. The immunomodulatory receptor T-cell immunoglobulin and ITIM domain (TIGIT) is typically coexpressed with PD-1 on CD8+ tumor-infiltrating T cells and inhibits T-cell activity and natural killer cell cytotoxicity. In preclinical models, targeting TIGIT demonstrated antitumor effects which were enhanced when combined with PD-1/PD-L1 inhibitors. Niu and colleagues, using the humanized immunoglobulin G1 monoclonal antibody targeting TIGIT vibostolimab (MK-7684), conducted a first-in-human phase I clinical trial in advanced solid tumors. Vibostolimab monotherapy or in combination with the PD-1 inhibitor pembrolizumab were evaluated for safety and tolerability as well as efficacy, with the trial split into two parts: part A being the dose-escalation and confirmation phase in confirmed metastatic solid tumors and part B expanding into specific tumor types and populations including NSCLC. In part A, no dose-limiting toxicities were observed in either the monotherapy or combination group, with the most common adverse events being rash, diarrhea, and adrenal insufficiency. Patients from the part A combination group also demonstrated unconfirmed increases in disease control rate as well as partial response. In part B, 106 patients with NSCLC were enrolled with anti–PD-1/PD-L1-naïve patients receiving combination therapy and anti–PD-1/PD-L1-refractory patients receiving either monotherapy or combination therapy. Adverse events in the anti–PD-1/PD-L1-naïve group included pyrexia and hypoalbuminemia while no patients in the monotherapy group experienced grade 3–4 adverse events. Those in the combination group exhibited decreased lymphocyte count and hypotension. Some patients in monotherapy and combination therapy did experience reduced target lesion size, with combination therapy in the naïve population showing the greatest effect. Treatment, however, was discontinued in a majority of patients due to progressive disease. Overall, this phase I study indicates promising antitumor activity of this combination therapy in patients with advanced solid tumors and those that are PD-1/PD-L1 inhibitor–naïve. Further investigation is warranted to continue evaluation of its efficacy.
Niu J, Maurice-Dror C, Lee DH, Kim DW, Nagrial A, Voskoboynik M, et al. First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small cell lung cancer. Ann Oncol 2021 Nov 17 [Epub ahead of print].
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