ProstAtak (aglatimagene besadenovec)

P2, N=57, Completed, The Methodist Hospital Research Institute | Active, not recruiting --> Completed

P2, N=90, Active, not recruiting, Candel Therapeutics, Inc. | Recruiting --> Active, not recruiting

P2, N=52, Completed, Candel Therapeutics, Inc. | Phase classification: P2a --> P2

We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

Dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy sparing strategy to enhance anti-tumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.

P1, N=36, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Apr 2023 --> Oct 2023

CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell's genome, thereby inflicting immunogenic cancer cell death. IL-12 synthesis likely depends on interactions with the tumor microenvironment, and it facilitates CAN-2409 cell killing. This dataset provides potential to understand resistance mechanisms and identify potential biomarkers for future studies.

P2, N=54, Active, not recruiting, Candel Therapeutics, Inc. | Recruiting --> Active, not recruiting

P2, N=86, Recruiting, Candel Therapeutics, Inc. | Trial completion date: Mar 2025 --> Dec 2026 | Trial primary completion date: Mar 2023 --> Dec 2024

P2, N=57, Active, not recruiting, The Methodist Hospital Research Institute | Trial primary completion date: Nov 2022 --> Jul 2022

Patients were evaluated for tumor response and abscopal effect.Median age was 69 years; 80% stage IV; 11% PD-L1 >50%; 80% receiving pembrolizumab and 20% nivolumab. Direct tumor injection of oncolytic virus in patients with advanced NSCLC and inadequate response to first-line ICI is well tolerated. Early data suggests that CAN-2409 treatment induces immunization against tumor antigens in the injected tumor and un-injected metastases.

The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated mTNBC patients. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

The expression of tk in transduced cancer cells results in conversion of the pro-drug ganciclovir into a toxic metabolite causing DNA damage, inducing immunogenic cell death and immune activation...We investigated the effects of ATR inhibitor AZD6738 in combination with CAN-2409 in vitro using cytotoxicity, cytokine, and fluorescence-activated cell sorting (FACS) assays in glioma cell lines and in vivo with an orthotopic syngeneic murine glioma model...In a tumor re-challenge, long-term immunity after combination treatment was not improved. Our results suggest that ATR inhibition could amplify CAN-2409's efficacy in glioblastoma through increased DNA damage while having complex immunological ramifications, warranting further studies to determine the ideal conditions for maximized therapeutic benefit.

P2, N=57, Active, not recruiting, The Methodist Hospital Research Institute | Trial primary completion date: May 2022 --> Nov 2022

Temozolomide is administered to MGMT-methylation positive patients only. CONCLUSIONS The combination of CAN-2409 + nivolumab + SOC was well tolerated. Clinical follow-up and extensive biomarker analyses will provide a better understanding of the therapeutic potential of this approach.

P2, N=57, Active, not recruiting, Jenny C. Chang, MD | Recruiting --> Active, not recruiting

Valacyclovir was administered for 14 days, starting the day after AdV-tk injection. Intratumoral injection of AdV-tk into lung tumors was safe and feasible. Further, AdV-tk effectively induced peripheral blood and intra-tumoral CD8 T cell activation. Consequent upregulation of inhibitory receptors suggests a potential benefit for combination therapies.