The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed...All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.

P2, N=42, Recruiting, Soligenix | Trial completion date: Dec 2023 --> Jun 2025 | Trial primary completion date: Oct 2023 --> Apr 2025

P=N/A, N=13, Active, not recruiting, Fundació Sant Joan de Déu | Recruiting --> Active, not recruiting | Phase classification: P1 --> PN/A | Trial completion date: Jun 2022 --> Jul 2024 | Trial primary completion date: Jun 2022 --> Jun 2024

P1, N=18, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the clinical efficacy and patient survival of viroimmunotherapy treated animals.

P1, N=30, Suspended, DNAtrix, Inc. | Trial completion date: Dec 2023 --> Dec 2026 | Recruiting --> Suspended | Trial primary completion date: Jul 2022 --> Jul 2026

P2, N=109, Active, not recruiting, Promontory Therapeutics Inc. | Recruiting --> Active, not recruiting | N=180 --> 109

P2, N=60, Recruiting, Armata Pharmaceuticals, Inc. | Trial completion date: Feb 2024 --> Aug 2024 | Trial primary completion date: Feb 2024 --> Jul 2024

Critically, the effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity depend on the cytosolic signal transducer myeloid differentiation response gene 88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces DC maturation and hence elicits anticancer immunity, with important implications for the use of LTX-315 as an anticancer immunotherapeutic.

P1, N=25, Recruiting, Yana Najjar | Not yet recruiting --> Recruiting

P1, N=40, Not yet recruiting, China Medical University, China

P2, N=30, Not yet recruiting, China Medical University, China

P1, N=36, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2023 --> Sep 2027 | Trial primary completion date: Sep 2023 --> Sep 2027

P3, N=400, Not yet recruiting, Replimune Inc.

P1/2, N=29, Completed, Armata Pharmaceuticals, Inc. | Phase classification: P1b/2a --> P1/2

P1, N=20, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

P1, N=12, Not yet recruiting, Beijing Bio-Targeting Therapeutics Technology Co., Ltd

P1, N=25, Not yet recruiting, Yana Najjar

P1/2, N=50, Active, not recruiting, Provectus Biopharmaceuticals, Inc.

P2, N=96, Recruiting, Theriva Biologics SL | Phase classification: P2b --> P2

P3, N=426, Recruiting, CG Oncology, Inc. | Not yet recruiting --> Recruiting

P1/2, N=65, Recruiting, Replimune Inc. | Phase classification: P1b/2 --> P1/2

P1/2, N=57, Recruiting, Mayo Clinic | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

P1, N=9, Recruiting, Shanghai Yunying Medical Technology

Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.

P1/2, N=50, Recruiting, Armata Pharmaceuticals, Inc. | Phase classification: P1b/2a --> P1/2 | Trial completion date: Dec 2023 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Dec 2024

P2, N=10, Recruiting, Soligenix | Not yet recruiting --> Recruiting

Enadenotucirev, a chimeric HAdV-11p/HAdV-3 adenovirus identified by bio-selection, is a low seroprevalence vector active against a broad range of human carcinoma cell lines...However, this information is very important, as it has a direct influence on the effectiveness of HAdV-11-based vectors. The aim of this work is to determine which of the two receptors, DSG2 and CD46, is involved in the attachment of the virus to the host, and what role they play in the early stages of infection.

P2, N=10, Not yet recruiting, Soligenix

P1/2, N=50, Active, not recruiting, Provectus Biopharmaceuticals, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=192 --> 50

P1/2, N=68, Completed, Promontory Therapeutics Inc. | Active, not recruiting --> Completed | Phase classification: P1b/2a --> P1/2

Overall, these data suggest that an early and robust systemic adaptive immune response could be used as a biomarker for long term survival following DNX-2401 treatment of recurrent glioblastoma independent of other salvage treatments administered following disease progression during the trial. (Clinical Trial.gov registration: NCT02197169).

P2, N=20, Active, not recruiting, Lytix Biopharma AS | Recruiting --> Active, not recruiting

P3, N=426, Not yet recruiting, CG Oncology, Inc.

P2, N=50, Recruiting, Ellen Kim, MD | Not yet recruiting --> Recruiting

Furthermore, the suppression of Nanog-mediated stem cell-like features by Amcasertib was particularly pronounced in ER-negative ovarian cancer and cancer stem cells, highlighting its high anticancer efficacy in this subgroup. These results suggest that Amcasertib holds promise as a potential standalone or combination therapy agent for the treatment of ER-negative ovarian cancer.

A total of 91 pts are included in this analysis (initial melanoma cohort, 16 pts; R-D cohort, 75 pts; data cut: Dec 30, 2022). The overall objective response rate (ORR) was 37.4% (initial cohort, 37.5%; R-D cohort, 37.3%), and 18.7% of pts achieved complete response (CR; Table). The response rates seen were also encouraging when evaluated by prior anti–PD-1 therapy setting and disease stage (Table).

Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide. Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.

P1, N=24, Recruiting, West China Hospital

P1/2, N=51, Not yet recruiting, Institut Curie

CEDAR is the first trial to successfully combine an intravenous oncolytic adenovirus with radiation, demonstrating the feasibility and acceptability of this approach, and a new paradigm in radiosensitization in rectal cancer. Within this small Phase I study, EnAd demonstrated an acceptable safety profile with evidence of a higher-than-expected rate of response by mrTRG. Translation analysis of tissue, blood and microbiome for biological correlates of radiation synergy is underway.

Our data suggest that treatment with DNX-2401 followed by a short-course of dose-dense TMZ is feasible, can be safely administered with expected adverse events related to chemotherapy, and appears to render a clinical benefit in a subset of patients with recurrent GBM. Further assessment of this therapeutic approach is warranted.