P2, N=0, Withdrawn, TJ Biopharma Co., Ltd. | N=160 --> 0 | Trial completion date: Dec 2024 --> Dec 2023 | Suspended --> Withdrawn | Trial primary completion date: Jun 2024 --> Dec 2023

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2023 --> Jun 2024

Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).

P1, N=89, Recruiting, German Cancer Research Center | Not yet recruiting --> Recruiting

P2, N=219, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

B7-H3 may stabilize EGFR to activate its downstream pathway for cancer cell proliferation and resistance to oxaliplatin (OXP)...Overall, these results showed that B7-H3 exhibited a high prevalence in COAD patients and was significantly associated with worse prognosis in COAD patients. Dual targeting of B7-H3 and EGFR signaling might be a potential therapeutic strategy for high-risk COAD patients.

P2/3, N=52, Terminated, Y-mAbs Therapeutics | Trial completion date: Dec 2026 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: May 2026 --> Jun 2023; Corporate business decision. Not due to safety or efficacy concerns.

Particularly promising treatments are enoblituzumab for prostate cancer, 131I-omburtamab for central nervous system malignancies, and HS-20093 for small-cell lung cancer but further studies are warranted. These data will be telling of the efficacy of B7-H3 inhibitors in both hematologic and solid malignancies. This study aimed to compile available results of B7-H3 inhibitors in oncology clinical trials.

Alternatives to mutagenic therapies for brain tumors should be explored for patients with CPS. LITT paired with imaging surveillance is a logical strategy to ensure durable outcomes and mitigate treatment-related secondary neoplasms.

P2, N=62, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Oct 2029 --> Oct 2030 | Trial primary completion date: Oct 2028 --> Oct 2029

P1, N=220, Recruiting, Xencor, Inc.

P1, N=177, Terminated, Y-mAbs Therapeutics | N=120 --> 177 | Active, not recruiting --> Terminated; Corporate business decision. No safety or efficacy concerns.

P1/2, N=128, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Phase classification: P1 --> P1/2

P1, N=54, Terminated, Y-mAbs Therapeutics | Active, not recruiting --> Terminated; Corporate business decision. Not due to safety or efficacy concerns

P1, N=128, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

Comprehensive in vitro characterization revealed that targeting the membrane-proximal epitope Q179 of the B7-H3 molecule allowed for a 100-fold reduction of CD3 affinity in our lead compound CC-3 with preserved superior tumor cell killing, efficient T cell activation, proliferation and memory formation, whereas undesired cytokine release was reduced...The trial will consist of a dose escalation part with an accelerated and a standard titration phase to determine the maximum tolerated dose followed by a dose expansion part to define the recommended phase II dose and collect first signs of efficacy. Together, we report on the straight forward development of a novel optimized bsAb from bench to first clinical evaluation that holds promise to improve treatment of CRC patients.

Conclusions HK056–001, a B7H3×4–1BB bsAb with human IgG1 Fc fragment prevents tumor development by killing tumor cells directly via effector functions mediated by NK and cytotoxic T cells. These results indicate that this bsAb holds the potential to be developed as a novel clinical therapy for cancer types with B7H3 expression.

Exploratory objectives include analysis of intratumoral and peripheral PD, including markers of T-cell activation; expression of tumor/immune markers; ctDNA levels; and association of PK and/or PD with clinical outcome. Enrollment has begun.

P2, N=219, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

P1, N=89, Not yet recruiting, German Cancer Research Center

P1, N=0, Withdrawn, Y-mAbs Therapeutics | N=36 --> 0 | Not yet recruiting --> Withdrawn

In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti-PD-L1 treatment restored NK cell-mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. Based on our findings, we conclude that EBV infection can inhibit NK cell-mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell-based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.

P1, N=128, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

Epitope mapping revealed non-overlapping B7-H3 binding epitopes of 6B5 and Enoblituzumab. Taken together, these data suggest that 6B5 is a promising therapeutic anti-human B7-H3 IgG monoclonal antibody that may find clinical application in a range of cancers, including current refractory types.

In pan-human cancers, a high cytotoxic CD38CD39CD4 T-cell gene signature correlates with better clinical prognosis. These results show that mTORC1-hyperactivity, present in many human tumors including tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM), drives B7-H3 expression leading to suppression of cytotoxic CD4 T cells.

P1, N=54, Active, not recruiting, Y-mAbs Therapeutics | Trial completion date: Sep 2022 --> Sep 2023

P2, N=160, Suspended, I-Mab Biopharma Co. Ltd. | Initiation date: Dec 2022 --> Dec 2023 | Not yet recruiting --> Suspended

Additionally, in vitro experiments showed that knockdown of CD276 inhibited the proliferation of ovarian cancer (OV) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) cell lines. CD276 is a potent biomarker for predicting the prognosis and immunological features in some tumors, and it may play a critical role in the tumor immune microenvironment (TIME) through macrophage-associated signaling.

P2, N=62, Active, not recruiting, Pediatric Brain Tumor Consortium | Trial completion date: Jul 2030 --> Oct 2029 | Trial primary completion date: Jul 2027 --> Oct 2028

In addition to its role in immune modulation, B7-H3 also promotes pro-tumorigenic functions such as tumor migration, invasion, metastases, resistance, and metabolism. In this review, we will provide an overview of this newly characterized immune checkpoint molecule and its development in the management of metastatic NSCLC.

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2022 --> Jul 2023

B7-H3 TriKE may be particularly useful for patients with bone lesions or as consolidative therapy. Commercial manufacturing of B7-H3 TriKE (GTB-5550) has begun, and a phase I trial is expected in late 2023.

Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.

P2, N=62, Terminated, MacroGenics | Trial completion date: Apr 2024 --> Jul 2022 | Recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Jul 2022; Based on internal review of safety data

ATG-027 can also inhibit the interaction between PD1/PD-L1 to rescue T cell activity suppression. ATG-027’s dual T cell activation function and powerful ADCC, CDC, and ADCP properties contribute to its promising anti-tumor efficacy in preclinical models.

Results In preclinical studies, these multi-functional B7-H3 single-domain/1XX iPSC-derived CAR-T cells demonstrated improved tumor control compared to MGA271-scFv/1XX CAR-T cells...Conclusions Taken together, these results provide a tantalizing outlook for the effectiveness of multiplexed-engineered, iPSC-derived CAR-T cells targeting B7-H3, including in combination with therapeutic antibodies, for off-the-shelf treatment of solid tumors. Ethics Approval All animal experiments were reviewed and approved by Fate Therapeutics Animal Care Committee (IACUC) under the protocol 2019-11-01 O’Rouke.

Our data indicate that B7-H3 is overexpressed in AML and that an anti-B7-H3 antibody (T1-A5) not only blocks B7-H3's immunomodulatory function but also induces ADCC in AML cells in vitro and in vivo.

Our data indicate that B7-H3 is overexpressed in AML and that an anti–B7-H3 antibody (T1-A5) not only blocks B7-H3’s immunomodulatory function but also induces ADCC in AML cells in vitro and in vivo.

Ruxolitinib reduced B7H3 gene and protein expression and increased IL-2 and CD8 gene expression. These results suggest that ruxolitinib inhibition of B7H3 may restore exhausted T-cell activity in the MM BM tumor microenvironment.

P2, N=33, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2022 --> Sep 2022