P1, N=185, Completed, Trishula Therapeutics, Inc. | Active, not recruiting --> Completed

P2, N=180, Recruiting, Trishula Therapeutics, Inc. | Not yet recruiting --> Recruiting | Initiation date: Dec 2023 --> Mar 2024

ARL67156 activates NK cells through the vav1-Syk signaling pathway to enhance their cytotoxicity against gastric cancer cells, which may serve as a new strategy for NK cell immunotherapy for gastric cancer.

No abstract available

P2, N=180, Not yet recruiting, Trishula Therapeutics, Inc.

P1, N=81, Recruiting, Arcus Biosciences, Inc. | Trial completion date: Nov 2025 --> Aug 2025 | Trial primary completion date: Nov 2025 --> Aug 2025

P1, N=56, Completed, Trishula Therapeutics, Inc. | Active, not recruiting --> Completed

P1, N=85, Completed, Surface Oncology | Active, not recruiting --> Completed | N=177 --> 85

Clinically, high VISTA expression is associated with poor prognosis in patients with NSCLC. Altogether, our data provide deep insight into acquired resistance to RT from an immune perspective and present rational combination strategies.

P1, N=81, Recruiting, Arcus Biosciences, Inc. | Not yet recruiting --> Recruiting

Assessment of exploratory biomarkers is also planned. A Safety Review Committee will conduct evaluations on an ongoing basis and two interim analyses will be performed.

P2, N=70, Recruiting, Innate Pharma | Initiation date: Feb 2023 --> Jun 2023

P1, N=81, Not yet recruiting, Arcus Biosciences, Inc.

P1, N=56, Active, not recruiting, Trishula Therapeutics, Inc. | Trial completion date: Dec 2022 --> Dec 2023

The expression of CD39 on CD8 T cells in the CK region was higher in cancer tissue than in paracancerous tissue (p = 0.011), and high CD39-expressing CD8 T cells in the CK region (HR, 2.587; p = 0.033) and high CD39-expressing CD8 T cells in the CK region (HR, 3.090; p = 0.008) were independent risk factors for prognosis in ESCC patients; the expression of ENTPD1 was upregulated in ESCC tissues compared to normal tissues (adjusted p < 0.001; log fold change = 1.99), and its expression was significantly positively correlated with the expression of PDCD1, CTLA4, and HAVCR2. High CD39-expressing CD8 T cells can be used as a new molecular marker for the diagnosis and prognosis of ESCC, and the restoration of partially exhausted CD8 T cells by inhibiting CD39 may be a new strategy for treating ESCC.

P2, N=70, Recruiting, Innate Pharma

Importantly, inhibition of CD39 augmented in vivo anti-lymphoma effects by therapeutic antibodies including rituximab and daratumumab. Furthermore, the addition of a CD39 inhibitor to anti-CD20 and anti-CD47 combination therapy significantly improved survival in a disseminated model of aggressive B-cell lymphoma, supporting the benefit of dual targeting CD39-mediated eATP hydrolysis and CD47-mediated "don't eat me" signal. Together, preventing eATP degradation may be a potential approach to unleash macrophage-mediated anti-lymphoma immunity.

P2, N=40, Active, not recruiting, Surface Oncology | Recruiting --> Active, not recruiting | Trial completion date: Nov 2023 --> Jul 2023 | Trial primary completion date: Nov 2023 --> May 2023

P1, N=177, Active, not recruiting, Surface Oncology | Recruiting --> Active, not recruiting | Trial completion date: Nov 2022 --> Oct 2023 | Trial primary completion date: Oct 2022 --> Aug 2023

Furthermore, we found that S3I-201 displayed prominent anti-tumor efficacy in C3H/He OSCC mouse model via inhibiting CD39/CD73-adenosine signal pathway and decreasing MDSCs. These results suggest that STAT3 signal can induce the differentiation of monocytes into MDSCs in tumor microenvironment depending on CD39/CD73-adenosine signal pathway and STAT3 blockade is a promising therapeutic strategy for OSCC.

CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Moreover, cGAS expression in mouse KPC tumor cells was required for anti-tumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.

In addition, a significant synergistic effect is observed between CD39i and cisplatin, but the CD39i + anti-PD-L1 (or anti-PD1) strategy does not show any synergistic effects in the BC model. Our results confirm that CD39 is a potential target for the immune therapy of BC.

Targeting the Ado pathway has recently been reported to improve Durvalumab (D) efficacy in early-stage NSCLC patients, through the use of Oleclumab, an anti-CD73 mAb...Finally, in vivo, in a mouse tumor model engrafted in huCD39KI mice, moIPH5201 improved the anti-tumor efficacy of gemcitabine and anti-PD-L1 combination. Conclusions IPH5201 was shown to block CD39 enzymatic activity, to lower Ado and increase ATP levels in the TME and finally to improve anti-tumor efficacy in preclinical models. Altogether, the expression profile of CD39 in early stage NSCLC and preclinical combination data support the clinical evaluation of IPH5201 in combination with D and CT in early stage NSCLC patients.

Radiation and CD39 inhibition-induced ICD of glioma stem cells as a vaccine enhance CAR-T expansion in peripheral blood, multifunctionality in the TME, and antitumor effect in a glioma model. The multispecificity of CAR-T cells, targeting CAR and tumor antigens, vastly enhances the function of conventional CAR-T cells, stimulates a native immune response, and overcomes obstacles of specific antigen loss or low expression of target cells in antitumor therapy.

Results Real-time measurement of ATP showed the ability of oxaliplatin to induce ATP release in MC38 tumor cells in vitro . Relative percentages of the immune cells in the lymph nodes were unaffected, suggesting internalization or downregulation, not cellular depletion, as the mechanism for the decrease in cell-surface CD39. Conclusions Our results indicate the superb ability of AB598 to inhibit enzymatic activity and tumor growth in vivo and provide a rationale for the combination of CD39 inhibition with ICD-inducing chemotherapy in the clinic.

Additionally, numerous exhaustion markers such as LAG3, TIGIT, and CTLA4 were decreased on tumor in comparison to peripheral blood (p < 0.01). These results demonstrate the complex nature of immune signaling in GBM tumor microenvironment that our team continues to investigate.

CD39 inhibition might contribute to the effects of the powerful anticancer drug ceritinib. Ceritinib is a novel CD39 inhibitor with high metabolic stability and optimized physicochemical properties; according to our knowledge, it is the first brain-permeant CD39 inhibitor. Our discovery will provide the basis (i) to develop more potent and balanced dual CD39/ALK inhibitors, and (ii) to optimize the ceritinib scaffold towards interaction with CD39 to obtain potent and selective drug-like CD39 inhibitors for future in vivo studies.

P1, N=72, Recruiting, Suzhou Kebo Ruijun Biotechnology Co., Ltd

Restraining the function of NAMPT resulted in the functional improvement of effector CD8+ T cells by decreasing extracellular adenosine levels and inducing apoptosis of GC cells simultaneously. Therefore, this study demonstrates that NAMPT can be an effective target for gastric cancer immunotherapy.

The designed POL can effectively inhibit the growth of in situ, lung metastasis and postoperative recurrence melanoma model and form long-term immune memory. With the powerful clinical transformation potential of nanoliposome platforms, this new synergistic strategy is expected to enhance anticancer effects safely and effectively.

P1, N=172, Recruiting, Suzhou Kebo Ruijun Biotechnology Co., Ltd

Accordingly, CD39 enzymatic inhibition enhances SS cells viability and IL-2 production upon activation. These results strongly suggest a special caution for SS treatment with therapeutic inhibitors of CD39.

We developed a new humanized antibody that enhances anti-tumor immunity by inhibiting CD39 expressed on exhausted T cells and intra-tumor T cells. These data suggest the scientific rationale for the clinical development of BP1202 and their use in combination with ICIs, with ATP-adenosine pathway inhibitors, and with chemotherapies. BP1202 is currently being developed as a new antibody agent for cancer immunotherapy.

P1, N=56, Active, not recruiting, Trishula Therapeutics, Inc. | Trial completion date: Mar 2022 --> Dec 2022 | Trial primary completion date: Mar 2022 --> Nov 2022

CD73 inhibitor Adenosine 5'-(α,β-methylene)diphosphate also abrogated PMN suppressor function while using a different inhibitor (AB-680) had no effect...Together, these studies point to eATP as a modulator of PMN suppressor function in the TME and the potential to abrogate suppression by targeting CD39. Future studies will address the specific signaling functions of eATP on PMN in the TME that drive suppressor function.

The addition of nivolumab to chemotherapy has recently become the standard of care of 1st‑line (1L) treatment of locally advanced or metastatic (LA/M) gastric cancer but further improvements are needed. An expansion cohort of Study TTX‑030‑002 (ongoing, US and South Korea) is evaluating the safety and efficacy of the combination of TTX-030, budigalimab (anti-PD-1) and FOLFOX for the 1L treatment of patients (pts) with LA/M HER2− gastric/GEJ adenocarcinoma... Preliminary results indicate that the combination of TTX-030, budigalimab and FOLFOX exhibited promising efficacy as 1L treatment of LA/M gastric/GEJ cancer regardless of CPS status and has a manageable safety profile without evidence of excessive toxicities. To our knowledge, this represents the first report of an anti-CD39 antibody in combination with chemo-immunotherapy in gastric cancer. Updated clinical and biomarker data will be included in the final presentation.

P1, N=177, Recruiting, Surface Oncology | N=100 --> 177

Adriamycin (ADM) is able to promote the release of ATP, which recruits dendritic cells (DCs) to phagocytose GSCs...In mouse tumor models, the combination of ADM and CD39 blockade increased immune cell infiltration and reduced tumor size. These findings suggest that GSCs upregulate CD39 expression by their biological characteristics to maintain an immunosuppressive microenvironment, and CD39 inhibition supplies a favorable tumor microenvironment (TME) for immunotherapeutic intervention and enhances the immune response induced by chemotherapy.