DSB2455 / Duke Street Bio - LARVOL DELTA

Duke Street Bio Receives FDA Fast Track Designation for PARP1-Selective Inhibitor DSB2455 (Duke Street Bio Press Release) - "Duke Street Bio...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to DSB2455, its next-generation, CNS-active selective PARP1 inhibitor, for the treatment of patients with brain metastases originating from primary triple-negative breast cancer (TNBC) tumors harboring BRCA1/2 and/or homologous recombination repair (HRR) alterations....The compound is a next-generation, highly PARP1-selective inhibitor with demonstrated brain penetrance and potent anti-tumour activity in preclinical models of homologous recombination-deficient cancers, including brain metastases."

Evidence highlight • Fast track • Oncology • Triple Negative Breast Cancer • BRCA1 • BRCA2

Duke Street Bio Announces First Patient Dosed in Phase I Trial with DSB2455, a Next Generation PARP1 Selective Inhibitor for the Treatment of Solid Tumours (Duke Street Bio Press Release) - "Duke Street Bio Ltd...is pleased to announce that the first patient has been dosed in a Phase I trial evaluating the highly selective PARP1 inhibitor, DSB2455, in patients with solid tumours....The Phase Ia/Ib trial is a multi-centre adaptively designed dose escalation study with expansion cohorts to assess the safety, tolerability, and activity of DSB2455 as monotherapy or in combination with anti-cancer agents in participants with advanced malignancies."

Trial status • Breast Cancer • Castration-Resistant Prostate Cancer • Ovarian Cancer • Solid Tumor

Duke Street Bio Granted Approval by European Medicines Agency to Launch Next-Generation PARP1-Selective Inhibitor Trial (Duke Street Bio Press Release) - "Duke Street Bio Ltd...is pleased to announce that the European Medicines Agency (EMA) has granted approval to commence a clinical trial for its highly-selective PARP1 inhibitor, DSB2455. This potentially best-in-class, potent, highly selective and CNS-penetrant agent targets cancers that harbour homologous recombination deficiencies (HRD) including BRCA mutations...Preliminary data indicate a strong safety profile and compelling efficacy in preclinical studies, paving the way to open our trial in the clinic."

New trial • Oncology

Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Duke Street Bio Ltd | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Monotherapy • Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Profiling of PARP1-selective inhibitor DSB2455 in HR deficient and proficient cancer models as monotherapy and in combination (EORTC-NCI-AACR 2024) - "Furthermore, DSB2455 demonstrated excellent tolerability and superior anti-tumour efficacy over the first-generation PARP1/2 inhibitor olaparib when tested in combination with the HER2-directed and topoisomerase I inhibitor payload ADC, T-Dxd, in HRD CDX models. ConclusionsThese data demonstrate the potential for DSB2455 to improve treatment efficacy and support its clinical development both as monotherapy and as a chemo-sensitiser in combination with standard-of-care chemotherapy and targeted agents. The data also afford the opportunity to enable efficacy of DSB2455 in HR proficient settings, thus significantly expanding its therapeutic utility and patient reach."

Monotherapy • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA • HER-2 • PARP2

Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Duke Street Bio Ltd

Combination therapy • Metastases • Monotherapy • New P1 trial • Metastatic Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor