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Study to Assess Safety, Tolerability and Activity of DSB2455 in Participants With Advanced Malignancies
NCT06458712 · Duke Street Bio Ltd
In plain English
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Official title
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
About this study
Open label, multi-centre, Phase Ia/b adaptive design study with an initial 2-stage Dose Escalation Phase followed by a Dose Expansion Phase.
Eligibility criteria
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.
* Histologically confirmed diagnosis of locally advanced and/or metastatic breast cancer, prostate cancer (mCRPC), ovarian cancer, or pancreatic ductal adenocarcinoma (PDAC) with confirmed gene alterations/ mutations as defined in the protocol
* Has received prior cancer treatment as outlined in the protocol
* 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.
* 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, specific Cohort).
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 design
Enrollment target: 180 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-11-21
Estimated completion: 2028-12
Last updated: 2026-07-21
Interventions
Drug: DSB2455
Primary outcomes
- • 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. (Through study completion, an average of 1 year)
Sponsor
Duke Street Bio Ltd · industry
Contacts & investigators
ContactDuke Street Bio · contact · clinicaltrials@dukesb.com · +44 (0)203 890 8710
All locations (18)
Yale Cancer Center - Yale New Haven HospitalRecruiting
New Haven, Connecticut, United States
Tisch Cancer Institute Icahn School of Medicine at Mount SinaiRecruiting
New York, New York, United States
The University of Texas M. D. Anderson Cancer CenterRecruiting
Houston, Texas, United States
Institut BergonieRecruiting
Bordeaux, France
Institut GodinotRecruiting
Reims, France
Orszagos Onkologiai IntezetRecruiting
Budapest, Hungary
Centrum Terapii WspolczesnejRecruiting
Lodz, Poland
Uniwersytecki Szpital Kliniczny w PoznaniuRecruiting
Poznan, Poland
START La Rioja, Hospital Universitario San PedroRecruiting
Logroño, La Rioja, Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Spain
START Barcelona, CIOCC, Hospital Universitario Nou DelfosRecruiting
Barcelona, Spain
Hospital Universitario Reina SofíaRecruiting
Córdoba, Spain
Clinica Universidad de Navarra - MadridRecruiting
Madrid, Spain
Hospital 12 de OctubreRecruiting
Madrid, Spain
START Madrid-CIOCC, Hospital Universitario HM SanchinarroRecruiting
Madrid, Spain
Hospital Universitario Virgen de la VictoriaRecruiting
Málaga, Spain
Universitary Hospital Virgen del RocioRecruiting
Seville, Spain
Instituto Valenciano de OncologiaRecruiting
Valencia, Spain