Novel Immunotherapy Demonstrates Promising Results in Metastatic Cancer Trial
A new immunotherapy drug, designated 2141-V11, has shown important antitumor activity in a Phase 1 clinical trial involving patients with diverse metastatic cancers, according to research conducted at Rockefeller University. The drug, designed to activate CD40 receptors, proved ten times more potent in stimulating an antitumor immune response compared to previous iterations.
Historically, CD40-targeting drugs have been hampered by systemic toxicity due to the widespread presence of CD40 receptors on non-cancerous cells when administered intravenously. To mitigate this, researchers shifted to a direct intratumoral injection method.This localized approach resulted in only mild toxicity observed in trial participants.
The Phase 1 trial enrolled 12 patients with melanoma, renal cell carcinoma, and various types of breast cancer. Notably, none of the patients experienced the severe side effects commonly associated with other CD40-activating therapies. Six patients exhibited systemic tumor reduction, with two achieving complete remission – a complete disappearance of their cancer.
These complete remissions were observed in patients with melanoma and metastatic breast cancer, both cancers known for their aggressive nature and tendency to recur. In one melanoma patient with numerous metastases on the leg and foot, injection into a single tumor on the thigh led to the complete resolution of all tumors. A similar outcome was seen in the breast cancer patient, whose tumors in the skin, liver, and lung disappeared following injection into a skin tumor.
Analysis of tumor tissue samples revealed a substantial influx of immune cells, including dendritic cells, T cells, and mature B cells. These cells formed structures resembling tertiary lymphoid structures (TLS) within the tumors. TLS formation is linked to improved prognosis and responsiveness to immunotherapy.Remarkably, TLS were also detected in tumors that were not directly injected, indicating systemic immune cell migration following initial tumor targeting.
Building on these encouraging results, the ravetch lab is collaborating with researchers at Memorial Sloan Kettering and Duke University on several ongoing clinical trials (Phase 1 or Phase 2) investigating 2141-V11’s efficacy against specific cancers, including bladder, prostate, and glioblastoma. Nearly 200 patients are currently enrolled in these studies.
Researchers are now focused on identifying factors that predict patient response to the drug. Initial findings suggest a correlation between high T cell clonality at the start of treatment and successful remission.The team aims to understand the immune system characteristics necessary for the drug to be effective and perhaps convert non-responders into responders, addressing a major challenge in the field of immunotherapy where only 25-30% of patients typically benefit.
