Candel Therapeutics Reports Breakthrough Data for CAN-3110 in Recurrent Glioblastoma with Complete Pathological Response
核心洞察
Candel Therapeutics announced promising interim data from its phase 1b trial of CAN-3110 in recurrent glioblastoma (搜索), with one patient achieving complete pathological response.
A Science Translational Medicine publication revealed that CAN-3110 transforms the tumor microenvironment by replacing tumor cells with immune cells, though this appears as disease progression on MRI.
Updated survival data showed median overall survival of 11.8-12.0 months across treatment arms, with some patients surviving over 59 months after treatment.
Candel Therapeutics has reported encouraging interim data from its ongoing phase 1b clinical trial of CAN-3110 (linoserpaturev (搜索)) in recurrent glioblastoma (搜索), alongside a significant publication in Science Translational Medicine that reveals how the oncolytic viral immunotherapy transforms the tumor microenvironment in ways not detectable by conventional imaging.
Groundbreaking Findings Published in Science Translational Medicine
The research, published on October 8, 2025, was led by E. Antonio Chiocca, M.D., Ph.D., Executive Director of the Center for Tumors of the Nervous System at the Mass General Brigham Cancer Institute (搜索). The study analyzed 97 serial tumor biopsies from two patients treated with repeated administrations of CAN-3110 in Cohort C of the phase 1b clinical trial (NCT03152318).
The comprehensive analysis revealed a critical discordance between immune biomarkers and histologic evidence of response versus imaging results. Biopsy analyses demonstrated that CAN-3110 induced dynamic spatial and temporal remodeling of the tumor microenvironment, where tumor cells are replaced by immune cells. Remarkably, in one of the two patients, this process resulted in a complete pathological response.
"These data unveil a critical limitation in glioblastoma (搜索) clinical trials, demonstrating our inability to accurately assess efficacy of immunotherapies using conventional imaging," said Dr. Chiocca. "Through sophisticated analysis of serial biopsy samples, we showed that CAN-3110 can transform the tumor microenvironment. For the first time, we identified T cell clonotypes (搜索), specifically reactive against oncolytic HSV viral epitopes, alongside evidence for an antitumoral response, providing support for the dual mechanism of action of CAN-3110."
Immune Activation and Novel T Cell Response
Among the key discoveries, investigators reported the expansion of novel tissue-resident effector memory T cell clonotypes (搜索) specifically targeting CAN-3110 epitopes, together with the expression of HLA-presented immunopeptides (搜索), including cancer-associated antigens. These findings provide evidence for both viral- and tumor-specific immune activation after intra-tumoral injection of CAN-3110.
Interestingly, the study found that immune infiltration leads to an apparent increase in tumor size on MRI, which may be mistakenly interpreted as disease progression. These results underscore the limitations of conventional imaging in evaluating the response to viral immunotherapy and highlight the importance of overall survival data, supported by histology.
Updated Survival Data Shows Promising Outcomes
The company also reported updated survival data for all patients enrolled in the phase 1b clinical trial. Updated median overall survival was 11.8 months (CI: 8.3–14.9) for arm A (n = 41) and 12.0 months (CI: 10.0–NA) for arm B (n = 9), respectively, after a single injection of CAN-3110. At the time of data cutoff (8/15/2025), one patient from arm A and one patient from arm B were still alive after prolonged follow-up (59.2 and 42.4 months, respectively, after CAN-3110 administration).
In arm C, which involved multiple administrations, 9 patients had received repeated doses at the time of data cutoff. At the 1×10⁸ PFU dose, 3 patients received 4 injections, 1 patient received 5 injections, and 2 patients received 6 injections. At the 1×10⁷ PFU dose, 1 patient received 4 injections, and 2 patients received 5 injections. Median follow-up was 8.9 months.
Four out of 9 patients were alive at time of data cutoff (range 3.1-28.2 months after initiation of CAN-3110 treatment). Five patients had died, of which 3 died more than one year after initiation of CAN-3110 treatment (range 5.5-21.8 months). Importantly, there was no clear-cut evidence that more than 4 injections resulted in better clinical outcomes than 4 injections, suggesting that a larger number of CAN-3110 administrations may not be required to achieve optimal efficacy.
Clinical Significance and Future Plans
"Glioblastoma (搜索) is among the most difficult cancers to treat, with an expected median overall survival of less than 6 to 9 months in recurrent glioblastoma (搜索)," said Francesca Barone, M.D., Ph.D., Chief Scientific Officer of Candel. "The promising data presented today highlight the transformational potential of CAN-3110 in this indication, with OS in individual patients substantially exceeding historical benchmarks. These results support the notion that CAN-3110 could uniquely reprogram the cold, immunosuppressive tumor microenvironment, associated with extended survival."
Based on these encouraging results, Candel plans to design a small phase 2 clinical trial of CAN-3110 in recurrent glioblastoma (搜索), working closely with investigators, the glioblastoma (搜索) community, and regulators. CAN-3110 has previously received FDA Fast Track Designation and Orphan Drug Designation for the treatment of recurrent high-grade glioma (搜索).
About CAN-3110
CAN-3110 (linoserpaturev (搜索)) is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1 (搜索)) next-generation oncolytic viral immunotherapy candidate designed for dual activity for oncolysis and immune activation in a single therapeutic. The treatment was generally well tolerated with no dose-limiting toxicity reported in the clinical trial, with investigators observing improved median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition.