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

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

Overview

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

Interventions

• Drug DSB2455
  PARP1 selective inhibitor

Primary outcome measures

• Number of patients demonstrating dose limiting toxicities and SAEs [Time frame: Through study completion, an average of 1 year]
• Number of patients exhibiting reduction in tumor size. [Time frame: Through study completion, an average of 1 year]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 10 centers

• START La Rioja, Hospital Universitario San Pedro — Logroño
• Hospital Universitari Vall d'Hebron — Barcelona
• START Barcelona, CIOCC, Hospital Universitario Nou Delfos — Barcelona
• Hospital Universitario Reina Sofía — Córdoba
• Clinica Universidad de Navarra - Madrid — Madrid
• Hospital 12 de Octubre — Madrid
• START Madrid-CIOCC, Hospital Universitario HM Sanchinarro — Madrid
• Hospital Universitario Virgen de la Victoria — Málaga
• … and 2 more centers

United States · 3 centers

• Yale Cancer Center - Yale New Haven Hospital — New Haven
• Tisch Cancer Institute Icahn School of Medicine at Mount Sinai — New York
• The University of Texas M. D. Anderson Cancer Center — Houston

France · 2 centers

• Institut Bergonie — Bordeaux
• Institut Godinot — Reims

Poland · 2 centers

• Centrum Terapii Wspolczesnej — Lodz
• Uniwersytecki Szpital Kliniczny w Poznaniu — Poznan

Hungary · 1 center

• Orszagos Onkologiai Intezet — Budapest

Identifiers

NCT: NCT06458712 · DSB2455-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗