Candel Therapeutics' Breakthrough in High-Grade Glioma Treatment: A New Hope?

In the relentless battle against cancer, few diseases are as formidable as high-grade glioma, a particularly aggressive form of brain cancer. Despite advances in surgery, radiation, and chemotherapy, the prognosis for patients remains grim, with median survival rates hovering around 20 months. However, a recent publication by Candel Therapeutics offers a glimmer of hope, presenting data from a Phase 1b clinical trial that combines their investigational therapy CAN-2409 with the immunotherapy drug nivolumab and standard of care. The results, published in Neuro-Oncology, suggest that this novel approach could extend survival and activate the immune system in a subset of patients.



The trial, which enrolled 41 patients with newly diagnosed high-grade glioma, explored the safety and tolerability of CAN-2409 plus valacyclovir and nivolumab in addition to standard of care. The findings are intriguing: the median overall survival for the overall patient population was 15.1 months, but a subset of patients with methylated MGMT promoter and gross total tumor resection achieved a median survival of 30.6 months. This is a significant improvement over the typical survival rates for high-grade glioma patients, which are around 20 months for those without MGMT promoter methylation and about 2 years for those with it.

The immunological data from the trial is equally compelling. The treatment showed immune activation at weeks 3 and 5, including increased naive and effector T cells, and no dose-limiting toxicities were observed for CAN-2409. This suggests that the combination of CAN-2409 and nivolumab with standard of care is generally well tolerated and may extend survival in a subset of patients with evidence of local and systemic immune activation after experimental treatment.

The potential implications for future therapeutic strategies in this area are significant. The immunological data provides compelling mechanistic validation showing CAN-2409's ability to activate both local and systemic immune responses. The correlation between increased T-cell receptor diversity and improved survival outcomes supports CAN-2409's proposed mechanism of action as an in situ vaccination approach. This could lead to the development of companion diagnostics to identify patients most likely to benefit from this treatment.

While Candel is not pursuing CAN-2409 for high-grade glioma due to portfolio prioritization, the company is developing it for localized prostate cancer, pancreatic ductal adenocarcinoma, and non-small cell lung cancer. The favorable safety profile and immunological biomarker data suggesting potential patient selection strategies (based on immune cell composition) could accelerate development in their core indications. This publication effectively validates Candel's platform technology and suggests CAN-2409 could indeed function as a "pipeline in a product" across multiple solid tumors.

The key immunological and clinical biomarkers identified in the trial that could serve as predictors of patient response and survival include T cell receptor (TCR) diversity, immune cell composition, temporal pattern of immune activation, MGMT promoter methylation status, and gross total tumor resection. These biomarkers could be leveraged in future clinical trials and patient selection to develop companion diagnostics, biomarker-driven patient selection, dynamic monitoring, and personalized treatment strategies.

In conclusion, the Phase 1b clinical trial data on CAN-2409 and nivolumab in high-grade glioma patients offers a promising new avenue for treatment. While the results are preliminary and further research is needed, the potential for this combination therapy to extend survival and activate the immune system in a subset of patients is a significant development in the fight against this aggressive form of brain cancer. As Candel Therapeutics continues to develop CAN-2409 for other indications, the hope is that this novel approach could one day offer new hope to patients battling high-grade glioma and other solid tumors.