ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Design and Preclinical Evaluation of a Novel B7-H4-Directed Antibody-Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05123482 (A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors), which is not on this map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/IIa Multi-center, Open-label Master Protocol Dose Escalation and Expansion Study of AZD8205 as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (BLUESTAR)
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Safety and tolerability of PARP inhibitors in cancer patients: a network meta-analysis of randomized controlled trials.BMC cancer · 2026Pooled it
- Spatial proteomics deciphers the immune niche landscape of non-ampullary duodenal adenocarcinoma.British journal of cancer · 2026Article
- Expanding the therapeutic scope of PARP inhibitors in breast cancer: current indications and future directions.The Journal of clinical investigation · 2026Review
- HBO1 suppresses anti-tumor immunity of CD8⁺ T Cells in thyroid cancer by recruiting BRD4 to regulate VTCN1 expression.Cancer immunology, immunotherapy : CII · 2026Article
- B7-H4-targeted radiotheranostics enable precise imaging and potent therapy across solid tumor models.Science advances · 2026Article
- Advancements in Immune Checkpoint-Based Immunotherapy for Triple-Negative Breast Cancer.Current issues in molecular biology · 2026Review
- Antibody-Drug Conjugates in Solid Tumor Oncology and the Frontier of Precision Immunosuppression: A Mechanistic, Translational, and Clinical Review.International journal of molecular sciences · 2026Review
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Downregulation of B7-H4 contributes to the synergistic effect of USP2a-targeted/anti-PD-1 combination therapy in EGFR mutant lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Development and application of antibody-drug conjugates in gynecological cancers.Science China. Life sciences · 2026Review
- Clinical Significance of B7-H4 in Peripheral Blood of Patients With Myasthenia Gravis.Journal of immunology research · 2026Article
- B7-H4: a multifaceted immune checkpoint and oncoprotein in cancer biology and immunotherapy.Frontiers in immunology · 2026Review
- From dual inhibition to precision selectivity: the molecular rationale and clinical evolution of next-generation PARP1-selective inhibitors in solid tumors.Frontiers in oncology · 2026Review
- Derivation of AZD5335, a Novel FRα-Targeted TOP1i-Loaded ADC, for the Treatment of FRα-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Antibody-drug conjugates in cancer therapy: current landscape, challenges, and future directions.Molecular cancer · 2025Review
- Palmitoylation modulates antitumor immunity.Molecular biology reports · 2025Review
- Advances in Systemic Therapy for Ovarian Cancer Over the Past Decade: A Clinical and Molecular Perspective.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
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Authors and funding
32 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe evaluated the activity of AZD8205, a B7-H4-directed antibody-drug conjugate (ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination with the PARP1-selective inhibitor AZD5305, in preclinical models. EXPERIMENTAL
designIHC and deep-learning-based image analysis algorithms were used to assess prevalence and intratumoral heterogeneity of B7-H4 expression in human tumors. Several TOP1i-ADCs, prepared with Val-Ala or Gly-Gly-Phe-Gly peptide linkers, with or without a PEG8 spacer, were compared in biophysical, in vivo efficacy, and rat toxicology studies. AZD8205 mechanism of action and efficacy studies were conducted in human cancer cell line and patient-derived xenograft (PDX) models.
resultsEvaluation of IHC-staining density on a per-cell basis revealed a range of heterogeneous B7-H4 expression across patient tumors. This informed selection of bystander-capable Val-Ala-PEG8-TOP1i payload AZ14170133 and development of AZD8205, which demonstrated improved stability, efficacy, and safety compared with other linker-payload ADCs. In a study of 26 PDX tumors, single administration of 3.5 mg/kg AZD8205 provided a 69% overall response rate, according to modified RECIST criteria, which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models. Addition of AZD5305 sensitized very low B7-H4-expressing tumors to AZD8205 treatment, independent of HRD status and in models representing clinically relevant mechanisms of PARPi resistance.
conclusionsThese data provide evidence for the potential utility of AZD8205 for treatment of B7-H4-expressing tumors and support the rationale for an ongoing phase 1 clinical study (NCT05123482). See related commentary by Pommier and Thomas, p. 991.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.