P1, N=169, Active, not recruiting, AbbVie | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P1, N=162, Not yet recruiting, MediLink Therapeutics (Suzhou) Co., Ltd.

P3, N=468, Not yet recruiting, Daiichi Sankyo | Trial completion date: Jan 2028 --> Feb 2029 | Trial primary completion date: Jul 2026 --> Apr 2027

P2, N=17, Recruiting, Georgetown University | Not yet recruiting --> Recruiting

P2, N=260, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

P1/2, N=180, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

P1/2, N=149, Not yet recruiting, Daiichi Sankyo

P2, N=382, Active, not recruiting, MacroGenics | N=100 --> 382 | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2026 --> May 2027

P1/2, N=180, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

P1, N=610, Not yet recruiting, Hansoh BioMedical R&D Company

P2, N=260, Not yet recruiting, Daiichi Sankyo

P2, N=180, Recruiting, Daiichi Sankyo | N=91 --> 180 | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: May 2024 --> Jan 2025

P1, N=278, Recruiting, MacroGenics | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

P2, N=100, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=0, Withdrawn, Hansoh BioMedical R&D Company | N=50 --> 0 | Not yet recruiting --> Withdrawn

P2, N=50, Not yet recruiting, Hansoh BioMedical R&D Company | Initiation date: Nov 2023 --> Nov 2024

P2, N=170, Recruiting, Hansoh BioMedical R&D Company | Not yet recruiting --> Recruiting

P2, N=120, Recruiting, Hansoh BioMedical R&D Company | Not yet recruiting --> Recruiting | Initiation date: Sep 2023 --> Jan 2024

P2, N=220, Recruiting, Hansoh BioMedical R&D Company | Not yet recruiting --> Recruiting

P2, N=100, Not yet recruiting, MediLink Therapeutics (Suzhou) Co., Ltd.

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.

P2, N=17, Not yet recruiting, Georgetown University

P2, N=91, Recruiting, Daiichi Sankyo, Inc. | Active, not recruiting --> Recruiting

P3, N=468, Not yet recruiting, Daiichi Sankyo, Inc.

P2, N=100, Active, not recruiting, MacroGenics

P1/2, N=640, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd.

Vobra duo showed robust in vitro cytolytic activity against CD276 positive AML cells highlighting the need for ongoing preclinical evaluations of CD276 targeted therapies in AML. Given the established safety profile for vobra duo this provides a clear path for rapid translation to clinical use for high risk AML patients.

Here, we describe the development of a modified talirine PBD-based fully human CD276 ADC, called m276-SL-PBD, that is cross-species (human/mouse) reactive and can eradicate large 500-1,000-mm triple-negative breast cancer xenografts at doses 10- to 40-fold lower than the maximum tolerated dose. By combining CD276 targeting with judicious genetic and chemical ADC engineering, improved ADC purification, and payload sensitivity screening, these studies demonstrate that the therapeutic index of ADCs can be substantially increased, providing an advanced ADC development platform for potent and selective targeting of multiple solid tumor types.

Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC...Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.

Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.

Decitabine, a pan-DNMT inhibitor, attenuated tumor growth in NEPC patient-derived xenograft models, as well as retinoblastoma gene (RB1)-deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with RB1-proficient CRPC. DNMT inhibition may therefore be a promising therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3-low prostate cancer to DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis, and the development of biomarker-driven therapeutic strategies for these populations may ultimately help improve patient outcomes.

P2, N=100, Active, not recruiting, MacroGenics | Recruiting --> Active, not recruiting

P2, N=220, Not yet recruiting, Hansoh BioMedical R&D Company

P1, N=169, Active, not recruiting, AbbVie | Trial completion date: Nov 2023 --> Mar 2024 | Trial primary completion date: Nov 2023 --> Mar 2024

The toxicity study did not detect off-target immune toxicity or peripheral toxicity. Altogether, this study suggested that anti-CD276 ADC could be a promising candidate for NSCLC treatment.

Vobra duo exerts relevant antitumor activity in preclinical B7-H3-expressing NB models and represents a potential candidate for clinical translation.

P1/2, N=280, Recruiting, DualityBio Inc. | Not yet recruiting --> Recruiting

Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

N/A Now the trial is enrolling.

The study will enroll participants with mCRPC previously treated with one prior ARAT (abiraterone, enzalutamide, or apalutamide) for prostate cancer. One futility analysis based on PSA50 response rate will be performed for each arm after 20 evaluable patients are enrolled. Enrollment is ongoing.

B7-H3 expression was moderate to high in most patients; no correlation was observed between response and B7-H3 level, and an update will be presented at the congress. Table: 690P Efficacy Conclusions I-DXd continues to demonstrate a manageable safety profile and promising antitumor activity with encouraging DOR and OS in these heavily pretreated patients, which warrants further clinical evaluation across multiple indications.

Other parameters being measured include safety, pharmacokinetics, exposure-response, immunogenicity, and biomarkers. The estimated study completion date is November 2024.