Abstract
BackgroundMonoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Envafolimab, a humanized single-domain anti-PD-L1 antibody fused to an Fc fragment, represents a potential advance because it can be conveniently administered subcutaneously.MethodsThis open-label, single-arm, phase 2 study evaluated the efficacy and safety of envafolimab in patients with previously treated advanced dMMR/MSI-H tumors from 25 clinical sites across China. Adults with histologically confirmed locally advanced or metastatic malignant dMMR/MSI-H solid tumors received weekly 150 mg subcutaneous envafolimab injections in a 28-day treatment cycle. The primary efficacy endpoint was the objective response rate (assessed by a blinded independent review committee). Secondary efficacy outcomes were disease control rate, duration of response, progression-free survival, and overall survival.ResultsOne hundred and three patients (65 with colorectal cancer, 18 with gastric cancer, and 20 with other solid tumors) were enrolled. Median follow-up was 11.5 months. The objective response rate was 42.7% (95% confidence interval [CI] 33.0–52.8), and the disease control rate was 66.0% (95% CI 56.0–75.1). Median duration of response was not reached; the duration of response rate at 12 months was 92.2% (95% CI 77.5–97.4). Median progression-free survival was 11.1 months (95% CI 5.5 to not evaluable). Overall survival at 12 months was 74.6% (95% CI 64.7–82.1). Sixteen patients (16%) had at least one grade 3 or 4 related treatment-emergent adverse event. No grade 5 treatment-emergent adverse events related to envafolimab were reported. Injection site reactions, all grade 1–2, were reported in nine patients (9%), but there were no infusion reactions. Eight patients (8%) had grade 3 or 4 immune-related adverse events.ConclusionsThis is the first pivotal phase 2 study to examine the efficacy and safety of a single-domain immune checkpoint antibody in the treatment of cancer. Envafolimab was effective and had acceptable safety in the treatment of previously treated advanced dMMR/MSI-H solid tumors. As the first single-domain PD-L1-targeting antibody administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treatment of cancer.Trial registration ClinicalTrials.gov, NCT03667170. Registered 10 September 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03667170.
Highlights
Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion
Li et al J Hematol Oncol (2021) 14:95 administered by rapid subcutaneous injection, envafolimab has the potential to be a significant advance in the treat‐ ment of cancer
Pembrolizumab, nivolumab, and all other approved Programmed cell death protein 1 (PD-1)/PD-L1-targeting monoclonal antibodies are administered by intravenous infusion, which can be inconvenient for patients and increase utilization of medical resources, and in a minority of patients can cause life-threatening infusion reactions [10, 11]
Summary
Monoclonal antibodies targeting programmed death ligand 1 (PD-L1) signaling currently approved for defective mismatch repair (dMMR)/microsatellite instability high (MSI-H) tumors must be delivered by intravenous infusion. Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have emerged as attractive treatment options for various cancers. One of their applications is in the treatment of microsatellite instability high (MSIH) tumors, in which microsatellite sequences accumulate mutations due to defective mismatch repair (dMMR). Two PD-1-targeting monoclonal antibodies, pembrolizumab and nivolumab, have been approved in the USA for the treatment of metastatic dMMR/MSI-H CRC in patients who have failed standard chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan [10, 11]. Pembrolizumab, nivolumab, and all other approved PD-1/PD-L1-targeting monoclonal antibodies are administered by intravenous infusion, which can be inconvenient for patients and increase utilization of medical resources, and in a minority of patients can cause life-threatening infusion reactions [10, 11]
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