P1, N=150, Recruiting, BeiGene | Not yet recruiting --> Recruiting

P1, N=177, Recruiting, Shanghai Hansoh Biomedical Co., Ltd | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=460, Recruiting, Hansoh BioMedical R&D Company | Not yet recruiting --> Recruiting

P1, N=1048, Not yet recruiting, Hansoh BioMedical R&D Company

P1, N=319, Recruiting, Mersana Therapeutics | N=166 --> 319 | Trial completion date: Jan 2026 --> May 2027 | Trial primary completion date: Jan 2025 --> Dec 2026

P1, N=150, Not yet recruiting, BeiGene

P1, N=166, Recruiting, Mersana Therapeutics

These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC and provide evidence for activity of an ADC with a DNA-damaging payload in this population.

P1, N=400, Recruiting, Seagen Inc. | Active, not recruiting --> Recruiting | N=164 --> 400

The immune checkpoint ligand B7-H4 is a promising molecular target expressed by multiple solid tumors. SGN-B7H4V demonstrates robust antitumor activity in preclinical models through multiple potential mechanisms. Altogether, these preclinical data support the evaluation of SGN-B7H4V as a monotherapy in the ongoing phase 1 study of SGN-B7H4V in advanced solid tumors (NCT05194072) and potential future clinical combinations with immunotherapies.

P1, N=164, Active, not recruiting, Seagen Inc. | Recruiting --> Active, not recruiting | N=400 --> 164

Responses were observed at all tested dose levels and across various tumor types. Dose expansion in select tumor types is planned.

The patient achieving PR with the longest treatment duration of 403 days remains on treatment in 0.7 mg/kg cohort. Conclusions Based on data from the ongoing study, HS-20089 was well tolerated and showed antitumor activities in advanced solid tumors, with encouraging clinical efficacy in TNBC.

In a panel of 28 breast cancer patient-derived xenografts (PDX), XMT-1660 demonstrated activity that correlated with B7-H4 expression. XMT-1660 has recently entered clinical development in a Phase 1 study (NCT05377996) in cancer patients.

Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.

XMT-1660 is a B7-H4-directed Dolasynthen antibody drug conjugate designed with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. NCT05377996. Clinical trial information: NCT05377996.

Two ADC delivering topoisomerase I (TOP1) poisons (Enhertu and Trodelvy) have recently been FDA-approved for Her2- and Trop2-expressing solid tumors. Two ADC delivering topoisomerase I (TOP1) poisons (Enhertu and Trodelvy) have recently been FDA-approved for Her2- and Trop2-expressing solid tumors. In a recent study, a TOP1-anti B7-H4 ADC was described and shown to be synergistic with a novel PARP1-selective inhibitor.

To further exploit the DNA damage elicited by the specific delivery of the TOP1i warhead, the combination of AZD8205 with a novel poly-ADP ribose polymerase 1 (PARP1) selective inhibitor, AZD5305, was investigated. These data demonstrate that AZD8205 is a promising therapeutic candidate for the treatment of B7-H4 positive solid tumors. A first in human phase I/IIa study in patients with advanced solid tumors is currently ongoing (NCT05123482).

These data support B7-H4 as an attractive ADC target for treatment of drug-resistant HGSOC.

No abstract available

The trial is currently enrolling patients. NCT05377996

This vedotin drug linker system has been clinically validated in multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, and tisotumab vedotin. Moreover, SGN-B7H4V in combination with an anti-PD1 agent led to improved antitumor activity and elicited durable immune memory. Altogether, these nonclinical data further support the evaluation of SGN-B7H4V as a monotherapy in the ongoing Phase 1 Study of SGN-B7H4V in Advanced Solid Tumors ( NCT05194072 ) and potential future clinical combinations with immunotherapies.

Trial in progress

Secondary objectives include assessing initial activity (objective response and progression-free survival by RECIST v1.1, and overall survival), pharmacodynamics, pharmacokinetics, and immunogenicity. The trial is currently recruiting and will enroll patients globally.

DOR, PFS, and OS will be estimated using the Kaplan–Meier method. Enrollment for Part A is ongoing in North America and is planned in Europe.

An in vivo efficacy study demonstrated that B7-H4 antibodies significantly inhibited tumor growth in B-hB7-H4 mice bearing tumors derived from the B16-F10 murine melanoma line. These data confirm that the B-hB7-H4 humanized mouse model is a powerful tool for evaluating the preclinical potential of B7-H4-targeting immune-therapeutics.

These data suggest that AZD8205 is a promising therapeutic candidate for the treatment of B7-H4 positive solid tumors. A first in human phase 1 study in patients with advanced solid tumors is currently ongoing (NCT05123482).

XMT-1660 elicits a range of anti-tumor activity across a series of primary breast cancer xenograft models. XMT-1660 is currently in IND-enabling studies and is expected to enter a Phase I dose escalation clinical study in 2022. The efficacy/expression relationship of B7-H4 will be further evaluated in an upcoming clinical study with a goal to identify patients most likely to respond to XMT-1660.

This vedotin drug linker system has been clinically validated by multiple ADC programs, including brentuximab vedotin, enfortumab vedotin, tisotumab vedotin, and polatuzumab vedotin. Finally, SGN-B7H4V drove robust, curative activity in an immunocompetent tumor model as a monotherapy and paired well with an anti-PD1 agent. Altogether, these data support the evaluation of SGN-B7H4V as a monotherapy in a first-in-human phase 1 clinical study and potential future clinical combinations with immunotherapies.

P1, N=355, Recruiting, Seagen Inc. | Not yet recruiting --> Recruiting

P1, N=355, Not yet recruiting, Seagen Inc.