P1, N=91, Recruiting, GenVivo, Inc.

P1, N=61, Active, not recruiting, GenVivo, Inc. | Recruiting --> Active, not recruiting | N=122 --> 61 | Trial primary completion date: Dec 2023 --> Jun 2024

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

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

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.

P1, N=122, Recruiting, GenVivo, Inc. | Trial completion date: Mar 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

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.

Proximity labeling (PL) however, can also highlight transient and negative effects - those interactions which lead to dissociation from the existing protein complex. Here we highlight the power of PL in combination with recombinant KSHV to study viral host interactions.

Pharmacokinetic and pharmacodynamic effects of palbociclib were well characterized in Chinese patients with ABC. Despite higher exposure, pharmacokinetic parameters were similar to those of a previously studied non-Asian population. No palbociclib dose adjustment based on Chinese ethnicity is needed. Palbociclib-letrozole had a manageable safety profile.

We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response.

In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2, and TK1.

The D-Arg PEP in combination with cisplatin caused synergistic cell kill against prostate, breast, lung cancers, and the CCRF-CEM cell line. Marked synergy resulted when the D-Arg PEP was used in combination with pemetrexed against the lung adenocarcinoma cell lines. A xenograft study using the PL-PEP in combination with pemetrexed showed enhanced anti-tumor effects compared to each drug alone.

The FdUMP synthetic pathway was investigated by combining TP inhibitor (tipiracil hydrochloride; TPI) or RR inhibitor (hydroxyurea; HU) with 5FU...5FU metabolism and mechanisms of 5FU resistance are different in each cell line. Both synthesized FdUMP amount and FdUMP sensitivity should be considered in 5FU‑resistant cells.

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

Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The median survival of patients in the third cohort is 18.1 (range, 3.5-20.0) months. The study maximum tolerated dose (MTD) was not reached.

FT3 may be involved in proliferative signaling, as measured by TK1 activity, predominately in TN breast cancer.

Serial fluid sample testing following iNSC delivery showed the bimodal personalized therapy was well tolerated, with no iNSC-induced abnormal tissue pathology. Overall, this study lays an important foundation as this promising personalized cell therapy advances toward human patient testing.

P1/2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2020 --> Sep 2020

This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2- MBC patients treated with endocrine therapy and palbociclib.

The type of surgery had no impact on OS. Markers and hormonal status of liver metastases are important factors affecting prognosis.

Therapeutic efficacy of the immunostimulatory gene therapy strategy will be tested in the clinical arena in a Phase I clinical trial. We also discuss immunotherapeutic interventions currently being implemented in DIPG patients and discuss the profound therapeutic implications of immunotherapy for this patient populations.

We first describe the glioma model and the generation of neurospheres (NS) that express the surrogate antigen cOVA. Then, we describe functional assays to determine anti-tumor T-cell response.

These results suggest that GSK3β participates in the acquisition of gemcitabine-resistance by pancreatic cancer cells via impairment of the functional interaction between Rb tumor suppressor protein and E2F1 pro-oncogenic transcription factor, thereby highlighting GSK3β as a promising target in refractory pancreatic cancer. By providing insight into the molecular mechanism of gemcitabine resistance, this study identifies a potentially novel strategy for pancreatic cancer chemotherapy.

P1/2, N=34, Active, not recruiting, National Cancer Institute (NCI) | N=23 --> 34

In conclusion, IFIT2 knockdown enhances TS expression, which mediates 5-FU resistance, and SAHA pretreatment suppresses TS expression and hence sensitizes cells to 5-FU. SAHA will be an effective strategy for the treatment of OSCC patients with 5-FU resistance.

Significant variation was observed between the single biomarker test and their combination (Z test, p .

Additionally, the same synergistic effect can be seen on the promoter of cellular IL-10 gene. Overall, our data reveal an important role for Sp3 in the ORF50-mediated transactivation, and propose a new subclass of the ORF50-responsive elements in the viral and cellular promoters.

Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.

Intraperitoneal immunotherapy with JX restores peritoneal anticancer immunity and potentiates immune checkpoint blockade to suppress PC and malignant ascites in colon cancer.

A single intra-tumoral AdV-tk injection in three dose cohorts (maximum 10 viral particles) was performed during diagnostic staging, followed by a 14 day course of the prodrug valacyclovir, and subsequent surgery one week later...Thus, intratumoral AdV-tk injection into NSCLC proved safe, feasible, and effectively induced CD8 T cell activation. These data provide a foundation for additional clinical trials of GMCI for lung cancer patients with potential benefit if combined with other immune therapies.

P1/2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=35 --> 23

PROMISE (NCT0281902) is a prospective study enrolling women with HR-positive MBC starting palbociclib (Pb) + letrozole (L) (1 st line) or Pb + fulvestrant (2 nd line). Using a comprehensive “omics” approach, our data suggest that a secreted biomarker of proliferation (TK1) obtained prior to initiating CDK4/6i and ET for the first line treatment of HR+ MBC is associated with established and novel genes and pathways associated with prognosis of pts receiving ET and CDK 4/6i. Analysis of on-treatment (after 2 cycles) tumor RNA seq and its association with change in TK1 as well as data from the 2 nd -line cohort will be presented at the meeting.

Pts received PAL 125 mg daily, 5 on/2 off weekly, plus letrozole (LET) or fulvestrant (FUL) per physician choice, on a 28-day cycle (C). The Alt Dose Pal trial met its primary endpoint with reduced G3+ ANC. The efficacy data is comparable to prior reports. sTK1 shows promise for PAL response prediction and monitoring.

Importantly, combining our suicide gene therapy with standard chemotherapy agents used in the treatment of rhabdomyosarcoma, reduced the effective drug dose, diminishing deleterious side effects/patient burden. This modified, highly ARMS-specific promoter could provide a new therapy option for this difficult-to-treat cancer.

Bioluminescence and PET imaging of B7H3-sr39tk CAR T-cells confirmed complete tumor ablation with intraperitoneal GCV administration. This imaging and suicide ablation system can provide insight into CAR T-cell migration and proliferation during clinical trials while serving as a suicide switch to limit potential toxicities.