Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies

Phase Ia/Ib Open Label, Multi-Centre Dose Escalation Study With Expansion Cohorts to Assess the Safety, Tolerability, and Activity of DSB2455 as Monotherapy in Participants With Advanced Malignancies

Open label, multi-centre, Phase Ia/b adaptive design study with an initial 2-stage Dose Escalation Phase followed by a Dose Expansion Phase.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignancies With Homologous Recombination Deficiency (HRD) (Breast, Ovarian, mCRPC, Pancreatic Ductal Adenocarcinoma (PDAC), Brain Metastases)
• Intervention / Treatment: Drug: DSB2455

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Duke Street Bio; Phone Number: +44 (0)203 890 8710; Email: clinicaltrials@dukesb.com

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • Institut Bergonie
    • Contact: Principal Investigator; Phone Number: +33 5 56 33 33 33; Email: d.teyssonneau@bordeaux.unicancer.fr
  • Reims, France, 51100
    • Recruiting
    • Institut Godinot
    • Contact: Principal Investigator; Phone Number: +33326504111; Email: camille.mazza@reims.unicancer.fr
• Hungary
  • Budapest, Hungary, 1122
    • Recruiting
    • Orszagos Onkologiai Intezet
    • Contact: Principal Investigator; Phone Number: +3612248600/3211; Email: galgoczy.tunde@oncol.hu
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Principal Investigator; Phone Number: +3493 489 30 00; Email: comunica@vhir.org
  • Barcelona, Spain
    • Recruiting
    • START Barcelona, CIOCC, Hospital Universitario Nou Delfos
    • Contact: Principal Investigator; Phone Number: +34 93 254 50 30; Email: tatiana.hernandez@start-barcelona.com
  • Córdoba, Spain
    • Recruiting
    • Hospital Universitario Reina Sofía
    • Contact: Principal Investigator; Phone Number: +34 957 011 464; Email: asuncion.aranda21@gmail.com
  • Madrid, Spain
    • Recruiting
    • Hospital 12 de Octubre
    • Contact: Principal Investigator; Phone Number: +34 91 390 80 00; Email: gdevelasco.gdv@gmail.com
  • Madrid, Spain
    • Recruiting
    • START Madrid-CIOCC, Hospital Universitario HM Sanchinarro
    • Contact: Principal Investigator; Phone Number: +34917567825; Email: information@startresearch.com
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen de la Victoria
    • Contact: Principal Investigator; Phone Number: +34 671 594 566; Email: fasestempranas@ibima.eu
  • Seville, Spain, 41013
    • Recruiting
    • Universitary Hospital Virgen del Rocio
    • Contact: Principal Investigator; Phone Number: +34 62 867 82 09; Email: afalconglez@gmail.com
  • Valencia, Spain, 46009
    • Recruiting
    • Instituto Valenciano de Oncologia
    • Contact: Principal Investigator; Phone Number: +34961114000; Email: dlorente@fivo.org
  • La Rioja
    • Logroño, La Rioja, Spain, 26006
      • Recruiting
      • START La Rioja, Hospital Universitario San Pedro
      • Contact: Principal Investigator; Phone Number: +34 941 27 87 60; Email: maria.demiguel@startrioja.com
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center - Yale New Haven Hospital
      • Contact: Principal Investigator; Phone Number: 203-785-4069; Email: ingrid.palma@yale.edu
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Tisch Cancer Institute Icahn School of Medicine at Mount Sinai
      • Contact: Principal Investigator; Phone Number: 212-824-7945; Email: Jordan.Cuevas@mssm.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas M. D. Anderson Cancer Center
      • Contact: Principal Investigator; Phone Number: 713-563-1784; Email: tyap@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant (or legally acceptable representative, if applicable) provides written informed consent for the study.
• Aged ≥18 years of age on the day of signing the informed consent.
• Has measurable disease per RECIST v1.1, or non-measurable disease as defined in the protocol.
• ECOG performance status of 0 to 1.
• Life expectancy >12 weeks.
• Adequate organ function as defined in the protocol.
• Willing and able to comply with scheduled visits (including follow-up visits), and protocol procedures.
• Willing and able to undergo imaging procedures as per protocol.
• Willing to provide blood samples for correlative research purposes.
• Able to swallow oral medication as an intact dosage form.
• Prior intervention with an approved non-selective PARP inhibitor is permitted in Dose Escalation only.
• Histologically confirmed diagnosis of locally advanced and/or metastatic breast cancer, prostate cancer, ovarian cancer, or pancreatic ductal adenocarcinoma with confirmed gene alterations as defined in the protocol.
• Has received prior cancer treatment as outlined in the protocol, dependent on disease type.
• Known asymptomatic or symptomatic brain metastasis, as confirmed by an MRI brain scan, from a primary tumour and meeting the eligibility for the disease types noted above (Dose Expansion only).

Exclusion Criteria:

• Myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) or features suggestive of MDS/AML.
• Has received a prior PARP1-selective inhibitor.
• Has received prior systemic anti-cancer therapy including investigational agents or device within 2 or 4 weeks prior to study intervention, dependent on the treatment.
• Received prior radiotherapy within 2 weeks of the start of study intervention or has a history of radiation pneumonitis.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Note: administration of killed vaccines are allowed.
• Has had an allogeneic tissue/solid organ transplant.
• Has an active autoimmune disease that has required systemic intervention in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Refractory nausea and vomiting, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs.
• Undergone major surgery, open biopsy or significant traumatic injury ≤28 days prior to starting study intervention.
• Has an active infection requiring systemic therapy or an uncontrolled concurrent illness.
• Known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by the local health authority.
• Known history of Hepatitis B or known active Hepatitis C virus (HCV)
• Cirrhosis of the liver.
• Clinically significant pulmonary illness.
• Impaired cardiac function or clinically significant cardiac disease.
• Participants with a healing, serious or open wound, ulcer, or bone fracture within 28 days prior to first dose of study intervention.
• History or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participants involvement for the full duration of the study.
• A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to starting the study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Weight loss of >5% in the 8-week period prior to starting study intervention.
• Known allergy or hypersensitivity to any of the formulation components of DSB2455.
• Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of study intervention.
• Other disease-specific criteria as outlined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSB2455 Dose Escalation & Expansion	Drug: DSB2455; PARP1 selective inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients demonstrating dose limiting toxicities and SAEs	Number of patients demonstrating dose limiting toxicities and SAEs	Through study completion, an average of 1 year
Number of patients exhibiting reduction in tumor size.	Objective Response Rate (ORR)	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Duke Street Bio Ltd
• Investigators: Principal Investigator: Johann de Bono, MB ChB FRCP, Institute of Cancer Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Kenny-Caffey syndrome, Type 1; Anophthalmia with pulmonary hypoplasia
• Other Study ID Numbers: DSB2455-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No